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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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Kamran Aghayev, Frank Vrionis and Marc C. Chamberlain

Primary spinal cord tumors represent 4.5% of all central nervous system neoplasms. They are either intradural intramedullary or intradural extramedullary. Intramedullary tumors are predominantly intrinsic gliomas (astrocytomas and ependymomas). Spinal ependymomas can usually be completely removed by separating the tumor from the spinal cord and, when complete, no further therapy is required. Astrocytomas, by contrast, infiltrate the myelon, and therefore surgery is frequently incomplete. Intradural extramedullary tumors are mostly benign (WHO grade 1) and comprise either peripheral nerve sheath tumors (neurofibromas and schwannomas) or meningiomas. Complete resection can be performed on both lesions and is often curative. Radiotherapy is indicated for primary malignant tumors (WHO grade 3 and higher) and for patients in whom surgery is contraindicated. For grade 1 and 2 tumors, the role of radiotherapy is controversial. Chemotherapy is reserved for recurrent primary spinal cord tumors with no other options. However, the lack of clinical trials for these tumors is problematic. Consequently, treatment is similar to that for intracranial histologies. Early recognition of the signs and symptoms of primary spinal cord tumors facilitates early treatment, potentially minimizes neurologic morbidity, and improves outcome. Primary treatment for almost all spinal cord tumors is surgery, with predictors of outcome being preoperative functional status, grade of tumor, and extent of resection.

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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.