High-Grade Gliomas
High-Grade Gliomas Key Points
Incidence
There are approximately 68,000 new cases of brain tumors diagnosed in the United States each year. Gliomas now account for nearly 80% of malignant brain tumors. Glioblastoma (GBM) is the most common primary malignant brain tumor.
Biologic Characteristics
A better prognosis is associated with grade III tumors (as classified by the World Health Organization [WHO]) when compared with grade IV tumors (i.e., GBM) and for oligodendrogliomas when compared with astrocytomas. A better response to therapy and higher rates of survival are associated with oligodendroglial tumors manifesting 1p19q codeletions and IDH mutations. Methylation of the promoter for the MGMT gene predicts for increased sensitivity to DNA alkylating agents such as temozolomide and is prognostic for overall survival (OS) in patients with GBM, especially older patients.
Staging Evaluation
Optimal imaging is carried out with contrast-enhanced magnetic resonance imaging (MRI). Computed tomography (CT) scans are primarily used as an infrastructure for radiation treatment planning before fusion with MRI images. On the first postoperative day, an MRI study should be obtained to evaluate the extent of resection and as a basis for radiation treatment planning.
Primary Therapy and Results
The standard of care for the definitive treatment of newly diagnosed GBM in patients aged 18 years to 70 years is the delivery of approximately 60 Gy of fractionated partial brain radiotherapy following maximal safe surgical debulking. Irradiation (most commonly administered with conformal strategies) should be accompanied by concurrent temozolomide chemotherapy. Adjuvant temozolomide is also administered for at least 6 months following the end of radiotherapy unless disease progression occurs.
Temozolomide has not been established as a component of standard therapy for newly diagnosed WHO grade III gliomas; ongoing trials are investigating this issue.
Prospective randomized trials could not define a role for either brachytherapy or radiosurgery in the initial management of high-grade gliomas.
Locally Advanced Disease and Recurrence
Bevacizumab has been approved for salvage of failures following definitive therapy for GBM. If chemotherapeutic options are not available in the setting of recurrence, creative radiotherapeutic strategies (e.g., radiosurgery, intensity-modulated radiation therapy [IMRT], brachytherapy) may be considered.
High-grade gliomas are almost universally fatal. Although recently discovered combined-modality approaches have prolonged survival, many patients succumb relatively quickly, and cure remains elusive for the majority.
New protocols have recently emerged after decades of limited progress in the management of these tumors. New chemotherapeutic drugs, such as temozolomide, have found application in GBM. Bevacizumab is effective in recurrent disease and prolongs radiographic disease control in first-line regimens. In the future, molecular profiling may also allow tailoring of specific treatment to the patients most likely to benefit.