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

Focal signs: 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
(inconclusive) [1]

Race
See Clinical 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 surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy with
temozolomide [2, 3]

Patients older than 70 years: Less aggressive therapy is sometimes considered, using radiation or
temozolomide alone [4, 5, 6]
Key points regarding radiotherapy for GBM include the following: [7, 8, 9]

The addition of radiotherapy to surgery increases survival. [10, 11]

The responsiveness of GBM to radiotherapy varies.
Interstitial brachytherapy is of limited use and is rarely used.
Radiosensitizers, such as newer chemotherapeutic agents, [12] targeted molecular agents, [13, 14] and
antiangiogenic agents [14] may increase the therapeutic effect of radiotherapy. [15]

Radiotherapy for recurrent GBM is controversial.

The optimal chemotherapeutic regimen for glioblastoma is not yet defined, but adjuvant chemotherapy appears
to yield a significant survival benefit in more than 25% of patients. [16, 1, 17, 18, 19, 20]
Agents used include the following:

Temozolomide
Nitrosoureas (eg, carmustine [BCNU])
Inhibitors of MGMT (eg, O6-benzylguanine)
Cisplatin
Bevacizumab (alone or with irinotecan) for recurrent glioma
Tyrosine kinase inhibitors (eg, gefitinib, erlotinib)
Investigational therapies (eg, gene therapy, peptide and dendritic cell vaccines, synthetic chlorotoxins,
radiolabeled drugs and antibodies [21, 22, 23, 24, 25, 26]
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 [27]
The extent of surgery (biopsy vs resection) has been shown in a number of studies to affect length of
survival. Surgical options include the following:

Gross total resection (better survival)

Subtotal resection
In some cases, stereotactic biopsy 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)