Neuro-Oncology

Bigner, Darell, D.

doi: 10.1093/neuonc/4.4.241pmid: N/A

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Woods, Stacy, A.;McGlade, C., Jane;Guha,, Abhijit

doi: 10.1093/neuonc/4.4.242pmid: 12356354

Abstract Malignant astrocytomas are characterized by extensive vascularization attributed to increased expression of the angiogenic cytokine vascular endothelial growth factor (VEGF). VEGF is elevated in astrocytomas under normal oxygen conditions and undergoes induction in hypoxic stress. Prior studies have shown that both the phosphatidylinositol 3-kinase (PI3-kinase) and MEK1/2 (MAPK/ERK kinase 1/2) pathways promote proliferation of astrocytoma cells and growth of astrocytic tumors. Whether these pathways regulate growth by modulating angiogenesis as well as proliferation is not clear. In this study, pharmacologic inhibitors were used to specifically inhibit PI3-kinase and MEK1/2 activity in human malignant astrocytoma cell lines, and their effects on VEGF expression were determined. Northern blot analysis of VEGF messenger RNA (mRNA) from cells treated with inhibitors demonstrated cell line-specific responses. The PI3-kinase pathway regulated both the normoxic expression and hypoxic induction of VEGF in 2 cell lines, whereas MEK1/2 regulated only the normoxic expression in the same 2 lines. The third cell line showed no change in VEGF mRNA with inhibition of either of these 2 pathways. This study suggests that modulation of signaling pathways implicated in proliferation of astrocytoma cell lines may have varying effects in vivo depending on the role these pathways play in regulating tumor angiogenesis. References Bouterfa, H.L., Sattelmeyer, V., Czub, S., Vordermark, D., Roosen, K., and Tonn, J.C. ( 2000 ) Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Anticancer Res. 20 , 2761 -2771. Damert, A., Ikeda, E., and Risau, W. 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Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A.R., Ryan, H.E., Johnson, R.S., Jefferson, A.B., Stokoe, D., and Giaccia, A.J. ( 2000 ) Loss of PTEN facilitates H1F-1–mediated gene expression. Genes Dev. 14 , 391 -396. Author notes The Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada (S.A.W., C.J.M., A.G.); andDepartment of Medical Biophysics (S.A.W., C.J.M., A.G.) andDivision of Neurosurgery (A.G.), University of Toronto, Toronto, Ontario, Canada © 2002 by the Society for Neuro-Oncology

Hukin,, Juliette;Siffert,, Joao;Velasquez,, Linda;Zagzag,, David;Allen,, Jeffrey

doi: 10.1093/neuonc/4.4.253pmid: 12356355

Abstract Our purpose is to describe the incidence and clinical features of leptomeningeal dissemination (LM) in children with progressive low-grade neuroepithelial tumor (LGN). We have continuously tracked all patients with primary CNS tumors since 1986. Satisfactorily followed data were obtained on 427 of the 588 patients with localized LGN at diagnosis between 1986 and 1998, 177 (42%) of whom developed progressive or recurrent disease. LM was identified in 13/177 (7%). The median age at initial diagnosis was 5 years and at LM diagnosis was 8.5 years. The primary tumor sites were diencephalon (6), brainstem (3), cerebellum (2), cerebrum (1), and spinal cord (1). The histologies were pilocytic astrocytoma (4), ganglioglioma (4), fibrillary astrocytoma (3), mixed glioma (1), and glioneurofibroma (1). Management included chemotherapy (2) or radiotherapy (3) or both (7); 1 patient received only radical resections of symptomatic lesions. The 5-year progression-free survival rates for patients with localized versus LM disease at recurrence were 22% (95% confidence interval [CI], 13%-25%) versus 15% (95% CI, 0.1%-36%), respectively (P = 0.28). The 5- and 10-year overall survival rates for patients with localized disease versus LM were 87% (95% CI, 82%-92%) and 83% (95% CI, 77%-89%) versus 68% (95% CI, 39%-91%) and 68% (95% CI, 39%-91%), respectively (P = 0.05). The 7% incidence of LM is a low estimate because patients were not routinely staged at recurrence. Tumors arising from the diencephalon appeared to predispose to LM; no other predisposing features were identified. We strongly urge that for optimum treatment planning all patients with recurrent LGN be staged with an enhanced spine and brain MRI before adjuvant therapy is initiated. The good survival of patients with LGN and LM reflects a more indolent disease than malignant CNS tumors with LM. References Brooks, P.C., Clark, R.A.F., and Cheresh, D.A. 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Gilbert, Mark, R.;Friedman, Henry, S.;Kuttesch, John, F.;Prados, Michael, D.;Olson, Jeffrey, J.;Reaman, Gregory, H.;Zaknoen, Sara, L.

doi: 10.1093/neuonc/4.4.261pmid: 12356356

Abstract Temozolomide is a novel second-generation oral alkylating agent with demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). A multicenter phase II trial was conducted to determine the efficacy and safety of temozolomide before radiotherapy in patients with newly diagnosed GBM and AA. Fifty-seven patients (51 adult, 6 pediatric) with newly diagnosed supratentorial GBM or AA were treated with temozolomide (200 mg/m2 per day for 5 consecutive days every 28 days) for a maximum of 4 cycles. All patients were then treated with external beam radiotherapy. Twenty-two patients (39%) achieved objective response, including 6 (11%) with complete response (CR) and 16 (28%) with partial response (PR). Additionally, 18 (32%) patients had stable disease (SD). Of 21 patients (18 adult, 3 pediatric) with AA, 2 (10%) achieved CR, 5 (24%) achieved PR, and 8 (38%) had SD. Among adult patients with AA, the median progression-free and overall survival rates were 7.6 and 23.5 months, respectively. Among 36 patients (33 adult, 3 pediatric) with GBM, 4 (11%) had CR, 11 (31%) had PR, and 10 (28%) had SD. The median progression-free and overall survival rates among adult patients with GBM were 3.9 and 13.2 months, respectively. Temozolomide was safe and well tolerated in adult and pediatric patients. Grades 3 and 4 adverse events were reported in 16 (28%) and 7 (12%) patients, respectively. Temozolomide was safe and effective in treating newly diagnosed GBM and AA before radiotherapy. This pre-irradiation treatment approach appears promising, but will require additional evaluation in comparative studies. References Azizi, S.A., and Miyamoto, C. ( 1998 ) Principles of treatment of malignant gliomas in adults: An overview. J. Neurovirol. 4 , 204 -216. 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Yung, W.K.A., Albright, R.E., Olson, J., Fredericks, R., Fink, K., Prados, M.D., Brada, M., Spence, A., Hohl, R.J., Shapiro, W., Glantz, M., Greenberg, H., Selker, R.G., Vick, N.A., Rampling, R., Friedman, H., Phillips, P., Bruner, J., Yue, N., Osoba, D., Zaknoen, S., and Levin, V.A. ( 2000 ) A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br. J. Cancer 83 , 588 -593. Author notes The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (M.R.G., J.F.K.);Brain Tumor Center at Duke University, Durham, NC 27710 (H.S.F.);University of California at San Francisco, San Francisco, CA 94143 (M.D.P.);Emory University, Atlanta, GA 30322 (J.J.O.);Children's National Medical Center, The George Washington University, Washington, DC 20010 (G.H.R.);Schering-Plough Research Institute, NJ 07033-1300 (S.L.Z.) © 2002 by the Society for Neuro-Oncology

Lang, Frederick, F.;Gilbert, Mark, R.;Puduvalli, Vinay, K.;Weinberg,, Jeffrey;Levin, Victor, A.;Yung, W.K., Alfred;Sawaya,, Raymond;Fuller, Gregory, N.;Conrad, Charles, A.

doi: 10.1093/neuonc/4.4.268pmid: 12356357

Wrensch,, Margaret;Minn,, Yuriko;Chew,, Terri;Bondy,, Melissa;Berger, Mitchel, S.

doi: 10.1093/neuonc/4.4.278pmid: 12356358

Abstract The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. 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Berger, Mitchel, S.

doi: 10.1093/neuonc/4.4.300pmid: N/A

Brain Tumors. Volume 2, Atlas of Operative Microneurosurgery. By John M. Tew, Jr., Harry R. van Loveren, and Jeffrey T. Keller. W.B. Saunders, Philadelphia, 2001. 441 pp. $299.00 ISBN 0-7216-5730-3 This content is only available as a PDF. © 2002 by the Society for Neuro-Oncology

Laterra, John, J.

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PRACTICAL NEURO-ONCOLOGY: A GUIDE TO PATIENT CARE. By Leslie D. McAllister, John H. Ward, Susan F. Schulman, and Lisa M. DeAngelis. Butterworth-Heinemann, Boston, 2002. 316 pp. $39.99 ISBN 0-7506-7180-7 This content is only available as a PDF. © 2002 by the Society for Neuro-Oncology

Asher, Anthony, L.

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BRAIN TUMORS, AN ENCYCLOPEDIC APPROACH. second edition. Edited by Andrew H. Kaye and Edward R. Laws, Jr. Churchill Livingstone, Philadelphia, 2001. 1052 pp. $260.00 ISBN 0-443-06426-1 (Illustrated) This content is only available as a PDF. © 2002 by the Society for Neuro-Oncology

doi: 10.1093/neuonc/4.4.308pmid: N/A

This content is only available as a PDF. © 2002 by the Society for Neuro-Oncology