New evidence-based treatment guidelines for the management of patients with newly diagnosed glioblastoma multiforme (GBM) have been issued for the first time by the Joint Tumor Section of the American Association of Neurological Surgeons and Congress of Neurological Surgeons.
The guidelines, published in seven articles as a supplement to the September issue of the Journal of Neuro-Oncology (2008;89:255–362), focus on five areas: (1) neuroradiological assessment; (2) surgical management, specifically the role of cytoreductive surgery; (3) diagnosis, and the role of neuropathology; (4) radiation therapy of pathologically confirmed newly diagnosed disease in adults; and (5) cytotoxic chemotherapy.
“A lot of the data in neuro-oncology is fragmented and not very well supported, and this was an attempt to review the available data and indicate what levels of evidence were available for many of the things we commonly do,” noted Patrick Y. Wen, MD, Director of the Neuro-Oncology Division of Brigham and Women's Hospital, Harvard Medical School, a coauthor of the chemotherapy guidelines.
Those recommendations were that there is Level I evidence (i.e., high-level, from at least one well-designed randomized controlled trial) for the use of concurrent and post-irradiation temozolomide for patients age 18 to 70 with adequate systemic health; and Level II (mid-level) evidence for the use of BCNU-impregnated biodegradable polymers for patients for whom craniotomy is indicated.
Level III (non-direct) evidence suggests the addition of temozolomide to radiation therapy as an option for patients over age 70 who have a Karnofsky performance status above 50. “For patients 70 or older with newly diagnosed GBM, temozolomide alone is a well-tolerated alternative to radiation therapy, and its benefit might be comparable to that obtained with radiation therapy alone,” the guidelines note, adding that radiation therapy followed by one of the nitrosoureas is recommended for patients who cannot receive temozolomide.
Dr. Wen and his coauthors Camilo E. Fadul, MD, of Norris Cotton Cancer Center (first author); Lyndon Kim, MD, of the National Cancer Institute; and Jeffrey J. Olson, MD, of the Emory Winship Cancer Institute Brain Tumor Program and Center for Skull Base Surgery, reviewed 2,400 articles from 1966 to 2007, focusing on current and post-irradiation chemotherapy, chemotherapy in the elderly, and interstitial chemotherapy.
“The encouraging results obtained with temozolomide offer hope that clinical research using cytotoxic chemotherapy will improve the dismal outlook associated with GBM,” the chemotherapy guidelines conclude.
The recommendations for neuroradiologic assessment of patients with newly diagnosed glioblastoma, written by Srini Mukundan, of Duke University, Chad Holder, of Emory, and Dr. Olson (a coauthor of all seven articles), are as follows:
- Level I: Whenever possible, it is recommended that magnetic resonance imaging with the addition of gadolinium contrast enhancement be used because it may make it possible to differentiate glioblastoma from other intrinsic tumors and secondary tumors.
- Level II: Computerized tomography with the addition of contrast material may provide data allowing differentiation of glioblastoma from other intrinsic tumors and secondary tumors.
- Level III: The addition of proton magnetic resonance spectroscopy to standard anatomic MRI provides details that may improve diagnostic accuracy. In addition, the use of perfusion MRI with determination of mean regional blood volume may give data that help separate the histologic characteristics of intrinsic tumors from one another.
For the surgery guidelines, coauthors Timothy C. Ryken, MD, Bruce Frankel, MD, Terrance Julien, MD, and Dr. Olson concluded that there is insufficient evidence to support a Level I recommendation.
The Level II recommendation, though, is that for newly diagnosed supratentorial malignant glioma in adults, “maximal safe resection” should be undertaken (i.e., the maximal cytoreductive procedure provided that postoperative neurological deficit can be minimized).
The Level III recommendation is that biopsy, partial resection, or gross total resection may all be considered in the initial management of malignant glioma depending on the patient's condition and the size and location of the tumor.
For the diagnosis guidelines, coauthors Daniel J. Brat, MD, of Emory University, Richard A. Prayson, MD, of the Cleveland Clinic, and Drs. Ryken and Olson cite Level I evidence that diagnosis should be based on the histopathologic review of tissue.
The Level II recommendation is that both frozen section and cytopathologic evaluation are recommended for intra-operative diagnosis, with consultation from a neuropathologist who specializes in brain tumor diagnosis recommended for problematic cases.
The Level III recommendation is for incorporation of clinical and radiographic information with the final pathologic diagnosis. In addition, the authors note, the criteria of the WHO classification of brain tumors are internationally recognized and can be used for establishing diagnosis, and that proliferation studies, such as those based on Ki-67/MIB-1 staining, and molecular genetic tests are recommended as adjuvant studies for classification and prognostication.
For the radiation therapy guidelines, John Buatti, MD, Drs. Ryken and Olson, Mark C. Smith, MD, Penny Sneed, MD, John H. Suh, MD, and Minesh Mehta, MD, gave Level I and II recommendations:
Level I is that radiation therapy is recommended for the treatment of newly diagnosed malignant glioma in adults, and that treatment schemes should include dosage of up to 60 Gy given in 2 Gy daily fractions that includes the enhancing area. Hypo-fractionated radiation schemes may be used for patients with a poor prognosis and limited survival without compromising response, and that hyper-fractionation and accelerated fractionation have not been shown to be superior to conventional fractionation and are not recommended.
In addition, the guidelines caution, the use of brachytherapy or stereotactic radiosurgery as a boost to external-beam radiotherapy has not been shown to be beneficial and is not recommended in the routine management of newly diagnosed malignant glioma.
The Level II recommendation is that radiation therapy planning should include a margin of one to two cm around the radiographically defined T1 contrast-enhancing tumor volume or the T2 weighted abnormality on MRI.
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