Brain Cancer Treatment Protocols
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Safe surgical resection is the primary treatment for all grades of gliomas, a category of brain tumor whose most malignant grades are considered to be cancer. The surgical goal is gross total resection; less aggressive resection is employed for tumor potentially involving eloquent brain. Under certain circumstances, weighing risk versus benefit, expectant monitoring with serial imaging is used.
There is significant divergence of opinion on treatment approaches, particularly for grade II lesions, such as grade II astrocytoma. Radiation and chemotherapy regimens may vary among institutions. Those cited below represent treatment approaches from recent clinical trials. Seizure treatment or prophylaxis is commonly appropriate. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]
Information about treatment and clinical trials is available at https://virtualtrials.com.
Grade I (pilocytic astrocytomas):
These lesions are typically uncommon and noninvasive and are considered benign and potentially curable by surgery; when total surgical removal is not possible, radiation therapy or expectant management is typically employed
Grade II (low-grade infiltrative astrocytomas, oligodendroglioma, mixed gliomas):
Surgery is recommended for grade II with maximal safe resection
Unfavorable prognostic factors include age >40y, astrocytoma histology, largest dimension of tumor ≥ 6 cm, tumor crossing midline, and presence of neurologic deficit before resection; patients with up to 2 of these are considered low risk, while patients with 3 or more are high risk [13]
Low-risk patients should undergo observation, as well as patients who are ≤40 y; high-risk patients should be treated with fractionated external-beam radiation therapy (EBRT) or adjuvant chemotherapy [13]
The standard radiation dosage for low-grade astrocytomas is 45-54 Gy, delivered in 1.8 to 2.0 Gy fractions [13]
Adjuvant therapy includes temozolomide 150-200 mg/m2/day PO on days 1-5 of a 28-d cycle for six to eight cycles [14, 15]
Recurrences or progressive, low-grade disease (previously untreated): Temozolomide 75 mg/m2 PO daily on days 1-21 or 150-200 mg/m2 PO on days 1-5 of a 28-d cycle until disease progression or for a maximum of 24 cycles [15, 16]
Postoperative radiation therapy is often employed for unresectable, residual, or recurrent tumor
Chemotherapy is often used for low-grade oligodendrogliomas, particularly tumors with the 1p19q deletion, which is a marker for tumor susceptibility to chemotherapy [1, 2, 3]
Grade III (anaplastic astrocytoma or oligoastrocytoma):
The standard of care is surgical resection followed by EBRT (60 Gy in 30-35 fractions) and adjuvant temozolomide, 75 mg/m2/day PO on days 1-42, usually 1-1.5 h before radiation [6, 7, 8, 9]
Post–radiation therapy: Continue temozolomide at higher doses of 150-200 mg/m2/day PO on days 1-5 every 28 d or
PCV (procarbazine, lomustine, vincristine): lomustine (CCNU) 90-130 mg/m2 PO on day 1 plus procarbazine 60-75 mg/m2 PO on days 8-21 plus vincristine 1.4 mg/m2 IV (not to exceed 2 mg/dose) on days 8 and 29; administer every 6 wk for up to four cycles [4, 5, 6, 17] with deferred radiation therapy
Grade IV (glioblastoma):
The standard of care is surgical resection followed by EBRT (60 Gy in 30-35 fractions) and adjuvant temozolomide 75 mg/m2/day PO on days 1-42, usually 1-1.5h before radiation [6, 7, 8, 9, 18]
Postradiation therapy: Ccontinue temozolomide at higher doses of 150-200 mg/m2/day PO on days 1-5 every 28 d [19]
Consider the following:
Current avenues available include the following:
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Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May. 10(5):459-66. [Medline].
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National Comprehensive Cancer Network. Central Nervous System Cancers. V.2.2013. Available at http://www.nccn.org. Accessed: September 12, 2013.
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10. 352(10):987-96. [Medline].
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Heiland DH, Masalha W, Franco P, Machein MR, Weyerbrock A. Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine. J Neurooncol. 2015 Nov 27. [Medline].
Bokstein F, Blumenthal DT, Corn BW, Gez E, Matceyevsky D, Shtraus N, et al. Stereotactic radiosurgery (SRS) in high-grade glioma: judicious selection of small target volumes improves results. J Neurooncol. 2015 Nov 24. [Medline].
Ryu S, Buatti JM, Morris A, Kalkanis SN, Ryken TC, Olson JJ, et al. The role of radiotherapy in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2014 Jul. 118 (3):489-99. [Medline].
Jeffrey N Bruce, MD Edgar M Housepian Professor of Neurological Surgery Research, Vice-Chairman and Professor of Neurological Surgery, Director of Brain Tumor Tissue Bank, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University College of Physicians and Surgeons
Jeffrey N Bruce, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Neurological Surgeons, American Society of Clinical Oncology, Congress of Neurological Surgeons, New York Academy of Sciences, North American Skull Base Society, Pituitary Society, Society for Neuro-Oncology, Society of Neurological Surgeons
Disclosure: Received grant/research funds from NIH for other.
Benjamin Kennedy, MD Columbia University College of Physicians and Surgeons
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee
Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
Herbert H Engelhard, III, MD, PhD, FACS, FAANS Professor of Clinical Neurosurgery and Bioengineering, Chief, Division of Neuro-Oncology, Medical Director, UIC Neurosurgery Clinic, Department of Neurosurgery, University of Illinois at Chicago College of Medicine
Herbert H Engelhard, III, MD, PhD, FACS, FAANS is a member of the following medical societies: American Association for Cancer Research, American Association of Neurological Surgeons, American College of Surgeons, American Medical Association, American Society for Cell Biology, American Society of Clinical Oncology, Chicago Medical Society, Chicago Neurological Society, Congress of Neurological Surgeons, Illinois State Medical Society, North American Spine Society, Society for Neuro-Oncology, Society for Neuroscience
Disclosure: Nothing to disclose.
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