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Glioblastoma Multiforme

Practice Essentials

Glioblastoma multiforme (GBM) is the most common and most malignant of the glial tumors.
See the image below.

Histopathologic slide demonstrating a glioblastoma

Histopathologic slide demonstrating a glioblastoma multiforme (GBM).

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See Brain Lesions: 9 Cases to Test Your Management Skills, a Critical Images slideshow, to review cases including meningiomas, glioblastomas and craniopharyngiomas, and to determine the best treatment options based on the case history and images.

Signs and symptoms

The clinical history of a patient with glioblastoma multiforme (GBM) is usually short (< 3 months in > 50% of patients). Common presenting symptoms include the following:

Slowly progressive neurologic deficit, usually motor weakness

Headache

Generalized manifestations of increased intracranial pressure, including headaches, nausea and vomiting, and cognitive impairment

Seizures

Neurologic symptoms and signs can be either general or focal and reflect the location of the tumor, as follows:

General: Headaches, nausea and vomiting, personality changes, and slowing of cognitive function

Focal: Hemiparesis, sensory loss, visual loss, aphasia, and others

The etiology of GBM is unknown in most cases. Suggested causes include the following:

Genetic factors

Cell phone use (controversial)

Head injury, N-nitroso compounds, occupational hazards, electromagnetic field exposure (all inconclusive)

See Presentation for more detail.

Diagnosis

No specific laboratory studies are helpful in diagnosing GBM. Tumor genetics are useful for predicting response to adjuvant therapy.

Imaging studies of the brain are essential for making the diagnosis, including the following:

Computed tomography

Magnetic resonance imaging, with and without contrast (study of choice)

Positron emission tomography

Magnetic resonance spectroscopy

Cerebral angiography is not necessary

Other diagnostic measures that may be considered include the following:

Electroencephalography: May show suggestive findings, but findings specific for GBM will not be observed

Lumbar puncture (generally contraindicated but occasionally necessary for ruling out lymphoma)

Cerebrospinal fluid studies do not significantly facilitate specific diagnosis of GBM

In most cases, complete staging is neither practical nor possible. These tumors do not have clearly defined margins; they tend to invade locally and spread along white matter pathways, creating the appearance of multiple GBMs or multicentric gliomas on imaging studies.

See Workup for more detail.

Management

No current treatment is curative. Standard treatment consists of the following:

Maximal safe surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy with temozolomide

Patients older than 70 years: Less aggressive therapy is sometimes considered, using radiation or temozolomide alone

Supportive care for clinical manifestations (eg, headache, seizures, venous thromboembolism)

Surgical options include gross total resection (better survival), subtotal resection, and biopsy. Because GBM cannot be cured surgically, the surgical goals are as follows:

To establish a pathologic diagnosis

To relieve any mass effect

If possible, to achieve a gross total resection to facilitate adjuvant therapy

In some cases, stereotactic biopsy is followed by radiation therapy (eg, for patients with a tumor located in an eloquent area of the brain, patients whose tumors have minimal mass effect, and patients in poor medical condition who cannot undergo general anesthesia). The extent of surgery (biopsy vs resection) has been shown in a number of studies to affect length of survival.

Key points regarding radiotherapy for GBM include the following:

The addition of radiotherapy to surgery increases survival.

The responsiveness of GBM to radiotherapy varies.

Interstitial brachytherapy, in which radioactive seeds are placed intraoperatively, after tumor resection, allows immediate initiation of radiation therapy

Radiosensitizers, such as newer chemotherapeutic agents,
targeted molecular agents,
and antiangiogenic agents
may increase the therapeutic effect of radiotherapy.

Radiotherapy and/or radiosurgery for recurrent GBM is controversial.

The optimal chemotherapeutic regimen for GBM is not yet defined, but adjuvant chemotherapy appears to yield a significant survival benefit in more than 25% of patients.

Agents used include the following:

Temozolomide

Nitrosoureas (eg, lomustine, carmustine)

Bevacizumab (alone or with irinotecan) for recurrent cases

Tyrosine kinase inhibitors (eg, regorafenib, gefitinib, erlotinib)

Investigational therapies

See Treatment and Medication for more detail.

For patient education resources, see the Cancer Center as well as the patient education article Brain Cancer.

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