Glioblastoma and Other Primary Brain Malignancies in Adults: A Review

Abstract

Importance: Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%.

Observations: Approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P < .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation.

Conclusions and relevance: The incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals, and approximately 49% of primary malignant brain tumors are glioblastomas. Most patients die from progressive disease. First-line therapy for glioblastoma is surgery followed by radiation and the alkylating chemotherapeutic agent temozolomide.

Figure 1.. Symptoms of Malignant Brain Tumors related to the location of the tumor.

Highlighted in this image are symptoms that are related to the location of the tumor. In addition, patients with primary brain malignancies may experience generalized fatigue, seizures, and symptoms related to increased intracranial pressure, such as headache, nausea, vomiting, or papilledema.

Figure 2.. Imaging Features of Malignant Brain Tumors.

Representative MRIs from patients with glioblastoma, IDH-mutant low grade glioma, PCNSL, and malignant meningioma. Images include T1-weighted pre- and post-gadolinium and T2-weighted FLAIR. White arrows indicate vasogenic edema apparent on T2/FLAIR. Black arrow indicates ring-enhancement reflective of central necrosis often seen in glioblastoma. Yellow arrow indicates the dural attachment (“dural tail”) common with meningiomas.

Figure 3.. Integration of histological features and molecular alterations in the revised WHO Classification of Tumors of the Central Nervous System (CNS). Shown are examples for the most common “adult-type” diffuse gliomas.

^a This figure does not include pediatric-type diffuse high-grade gliomas which can present in adults. ^b Immunohistochemistry (IHC) with a highly sensitive and specific monoclonal antibody that recognizes the IDH1-R132H mutant protein is widely used. The IDH1-R132H mutation accounts for about 90% of all IDH1 and IDH2 mutations in supratentorial adult-type diffuse glioma. Testing for non–IDH1-R132H mutations uses DNA sequence analysis and is necessary when IHC for IDH1-R132H is negative. ^c IDH-wildtype glioblastomas lack mutations in IDH1 and IDH2. Absence of immunoreactivity for IDH1 R132H is sufficient to diagnose IDH-wildtype glioblastoma in patients aged 55 and older with histologically classic glioblastoma. ^d NEC: Not Elsewhere Classifiable. NEC designation indicates that appropriate diagnostic testing has been performed and results do not allow for an alternative diagnosis per World Health Organization criteria. Further molecular work up should exclude the presence of genetic findings that are associated with “pediatric-type” diffuse gliomas and circumscribed astrocytic gliomas.