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Matthias Holdhoff

The 2016 WHO Classification of Tumors of the Central Nervous System integrated molecular biomarkers into the classifications of malignant gliomas. Several markers now play a key role in our understanding of these tumors and are integral for clinical decision-making; these include codeletion of 1p and 19q and IDH1 and IDH2 mutations. The presentation by Matthias Holdhoff, MD, PhD, at the NCCN 23rd Annual Conference discussed the current understanding of anaplastic gliomas (WHO grade III) in the context of the new classification and its implications on clinical practice. The 2018 NCCN Guidelines for Central Nervous System Cancers incorporate molecular and histologic characteristics in the staging and treatment of both low- and high-grade gliomas (WHO grades II–IV).

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Matthias Holdhoff and Marc C. Chamberlain

Approximately half of all patients with glioblastoma are older than 65 years and nearly one-quarter are older than 70 years, with a rising incidence of this disease in the elderly population. The life expectancy of elderly patients with glioblastoma is significantly shorter than in younger patients. Potential explanations for this abbreviated survival include differences in tumor biology, reduced use of therapies, enhanced toxicity of treatment, or diminished efficacy of available therapies with increasing age. The current standard treatment of newly diagnosed, protocol-eligible, nonelderly patients with glioblastoma is based on the randomized prospective EORTC/NCIC study that included patients aged 18 to 70 years with a performance status of ECOG 0 to 2. Limited single-institution retrospective series suggest that clinically fit elderly patients may benefit from a similar treatment regimen. However, no randomized trial has been performed in the elderly population using this regimen. Available prospective randomized clinical trials in the elderly population with glioblastoma have shown that radiotherapy is superior to supportive care only, that single-modality hypofractionated radiotherapy (reduced dose and shorter treatment schedule) is an alternative to single-modality standard fractionated radiotherapy, and that single-agent temozolomide is equivalent to radiotherapy alone. This article summarizes published data of current patterns of care in elderly patients and reviews published evidence as it pertains to the benefit of different treatment modalities in elderly patients with glioblastoma. Notwithstanding the previously mentioned randomized trials, the optimal treatment of elderly patients with glioblastoma remains controversial.

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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.

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Louis Burt Nabors, Jana Portnow, Mario Ammirati, Joachim Baehring, Henry Brem, Nicholas Butowski, Robert A. Fenstermaker, Peter Forsyth, Jona Hattangadi-Gluth, Matthias Holdhoff, Steven Howard, Larry Junck, Thomas Kaley, Priya Kumthekar, Jay S. Loeffler, Paul L. Moots, Maciej M. Mrugala, Seema Nagpal, Manjari Pandey, Ian Parney, Katherine Peters, Vinay K. Puduvalli, John Ragsdale III, Jason Rockhill, Lisa Rogers, Chad Rusthoven, Nicole Shonka, Dennis C. Shrieve, Allen K. Sills Jr, Lode J. Swinnen, Christina Tsien, Stephanie Weiss, Patrick Yung Wen, Nicole Willmarth, Mary Anne Bergman and Anita Engh

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.