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David A. Reardon, Scott Turner, Katherine B. Peters, Annick Desjardins, Sridharan Gururangan, John H. Sampson, Roger E. McLendon, James E. Herndon II, Lee W. Jones, John P. Kirkpatrick, Allan H. Friedman, James J. Vredenburgh, Darell D. Bigner and Henry S. Friedman

Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth factor (VEGF), and generates blood vessels with distinctive features. The outcome for patients with recurrent glioblastoma is poor because of ineffective therapies. However, recent encouraging rates of radiographic response and progression-free survival, and adequate safety, led the FDA to grant accelerated approval of bevacizumab, a humanized monoclonal antibody against VEGF, for the treatment of recurrent glioblastoma in May 2009. These results have triggered significant interest in additional antiangiogenic agents and therapeutic strategies for patients with both recurrent and newly diagnosed glioblastoma. Given the potent antipermeability effect of VEGF inhibitors, the Radiologic Assessment in Neuro-Oncology (RANO) criteria were recently implemented to better assess response among patients with glioblastoma. Although bevacizumab improves survival and quality of life, eventual tumor progression is the norm. Better understanding of resistance mechanisms to VEGF inhibitors and identification of effective therapy after bevacizumab progression are currently a critical need for patients with glioblastoma.

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Steven S. Brem, Philip J. Bierman, Henry Brem, Nicholas Butowski, Marc C. Chamberlain, Ennio A. Chiocca, Lisa M. DeAngelis, Robert A. Fenstermaker, Allan Friedman, Mark R. Gilbert, Deneen Hesser, Larry Junck, Gerald P. Linette, Jay S. Loeffler, Moshe H. Maor, Madison Michael, Paul L. Moots, Tara Morrison, Maciej Mrugala, Louis Burt Nabors, Herbert B. Newton, Jana Portnow, Jeffrey J. Raizer, Lawrence Recht, Dennis C. Shrieve, Allen K. Sills Jr, Frank D. Vrionis and Patrick Y. Wen

OverviewIn 2010, an estimated 22,020 new cases of primary brain and other nervous system neoplasms were diagnosed in the United States,1 and approximately 13,140 deaths occurred from these tumors. The incidence of primary malignant brain tumors has been increasing over the past 30 years, especially in elderly persons.2 Metastatic disease to the central nervous system (CNS) occurs much more frequently, with an estimated incidence approximately 10 times that of primary brain tumors. Between 20% and 40% of patients with systemic cancer will develop brain metastases.3NOTE: This manuscript highlights only a portion of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System Cancers. Please refer to www.NCCN.org for the complete NCCN Guidelines.Principles of ManagementPrimary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. Primary brain tumors range from pilocytic astrocytomas, which are very uncommon, noninvasive, and surgically curable, to glioblastoma multiforme, the most common intraparenchymal brain tumor in adults, which is highly invasive and virtually incurable. Likewise, patients with metastatic brain disease may have rapidly progressive systemic disease or no systemic cancer at all. These patients may have one or dozens of brain metastases, and may have a malignancy that is either highly responsive or highly resistant to radiation or chemotherapy. Because of this marked heterogeneity, the prognostic features and treatment options for brain tumors must be carefully reviewed on an individual basis and sensitively communicated to each patient.In addition, CNS tumors are associated with...
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Louis Burt Nabors, Mario Ammirati, Philip J. Bierman, Henry Brem, Nicholas Butowski, Marc C. Chamberlain, Lisa M. DeAngelis, Robert A. Fenstermaker, Allan Friedman, Mark R. Gilbert, Deneen Hesser, Matthias Holdhoff, Larry Junck, Ronald Lawson, Jay S. Loeffler, Moshe H. Maor, Paul L. Moots, Tara Morrison, Maciej M. Mrugala, Herbert B. Newton, Jana Portnow, Jeffrey J. Raizer, Lawrence Recht, Dennis C. Shrieve, Allen K. Sills Jr, David Tran, Nam Tran, Frank D. Vrionis, Patrick Y. Wen, Nicole McMillian and Maria Ho

Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN. org, contains recommendations on additional subtypes.

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Louis Burt Nabors, Jana Portnow, Mario Ammirati, Henry Brem, Paul Brown, Nicholas Butowski, Marc C. Chamberlain, Lisa M. DeAngelis, Robert A. Fenstermaker, Allan Friedman, Mark R. Gilbert, Jona Hattangadi-Gluth, Deneen Hesser, Matthias Holdhoff, Larry Junck, Ronald Lawson, Jay S. Loeffler, Paul L. Moots, Maciej M. Mrugala, Herbert B. Newton, Jeffrey J. Raizer, Lawrence Recht, Nicole Shonka, Dennis C. Shrieve, Allen K. Sills Jr, Lode J. Swinnen, David Tran, Nam Tran, Frank D. Vrionis, Patrick Yung Wen, Nicole R. McMillian and Maria Ho

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.

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Louis Burt Nabors, Jana Portnow, Mario Ammirati, Joachim Baehring, Henry Brem, Paul Brown, Nicholas Butowski, Marc C. Chamberlain, Robert A. Fenstermaker, Allan Friedman, Mark R. Gilbert, Jona Hattangadi-Gluth, Matthias Holdhoff, Larry Junck, Thomas Kaley, Ronald Lawson, Jay S. Loeffler, Mary P. Lovely, Paul L. Moots, Maciej M. Mrugala, Herbert B. Newton, Ian Parney, Jeffrey J. Raizer, Lawrence Recht, Nicole Shonka, Dennis C. Shrieve, Allen K. Sills Jr, Lode J. Swinnen, David Tran, Nam Tran, Frank D. Vrionis, Stephanie Weiss, Patrick Yung Wen, Nicole McMillian and Anita M. Engh

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas.