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Glioblastoma Multiforme

Glioblastoma multiforme (GBM), also called glioblastoma, is a fast growing glioma that develops from star-shaped glial cells (astrocytes) that support nerve cells. GBM is classified as a grade IV astrocytoma. These are the most invasive type of glial tumors, rapidly growing, and commonly spread to nearby brain tissue. They may be composed of several different kinds of cells (i.e., astrocytes, oligodendrocytes). Sometimes they evolve from a low-grade astrocytoma or an oligodendroglioma. In adults, GBM occurs most often in the cerebral hemispheres, especially in the frontal and temporal lobes of the brain. GBM is a devastating brain cancer that typically results in death in the first 15 months after diagnosis.

GBMs are biologically aggressive tumors that present unique treatment challenges due to the following characteristics: 1) Localization of tumors in the brain; 2) Inherent resistance of these lesions to conventional therapy; 3) Limited capacity of the brain to repair itself; 4) Migration of malignant cells into adjacent brain tissue; 5) The variably disrupted tumor blood supply which inhibits drug delivery; 6) Tumor capillary leakage, resulting in peritumoral edema and intracranial hypertension; 7) A limited response to therapy; and 8) The neurotoxicity of treatments directed at gliomas.

Prevalence and Incidence

• An estimated 18,500 new cases of primary brain tumors were diagnosed in 2006; of these, 50 percent were glial and 50 percent of all gliomas were GBMs
• According to the Central Brain Tumor Registry in the US, 1- and 2-year survival in patients 65 or older is 13.3 and 2.1 percent, respectively
• More prevalent among people ages 50 to 70
• More common in men than women

Symptoms

Symptoms vary depending on the location of the brain tumor, but may include any of the following:

• Persistent headaches
• Double or blurred vision
• Vomiting
• Loss of appetite
• Changes in mood and personality
• Changes in ability to think and learn
• New seizures
• Speech difficulty of gradual onset

Diagnosis

Sophisticated imaging techniques can pinpoint brain tumors. Diagnostic tools include computed tomography (CT or CAT scan) and magnetic resonance imaging (MRI). Intraoperative MRI is also used during surgery to guide tissue biopsies and tumor removal. Magnetic resonance spectroscopy (MRS) is used to examine the tumor's chemical profile and determine the nature of the lesions seen on the MRI. Positron emission tomography (PET scan) can help detect recurring brain tumors.

Grading

After a brain tumor is detected on a CT or MRI scan, a neurosurgeon obtains tumor tissue for a biopsy and the tissue is examined by a neuropathologist. The analysis of tumor tissue under a microscope provides answers to the following two questions and is used to assign the tumor name/grade:

1) What type of brain cell did the tumor arise from? The name of the tumor is derived from this; for example, astrocytomas arise from star-shaped glial cells called astrocytes;

2) Are there signs of rapid growth in the tumor cells?

The tumor name/grade helps determine treatment options and also provides important information about prognosis.

Treatment Options

Supportive care only, without any active intervention or treatment, is an option for patients who are very disabled. Treatment options for others include surgery, radiation, radiosurgery, and chemotherapy. The main goal of surgery is to remove as much of the tumor as possible without injuring brain tissue needed for neurological function (such as the ability to speak, walk, motor skills, etc.). However, high-grade tumors are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it more difficult to remove the entire tumor. If the tumor cannot be completely removed, surgery can still reduce the amount of solid tumor tissue; remove those cells in the center of the tumor that may be resistant to radiation and chemotherapy; and reduce intracranial pressure. Debulking surgery can prolong the lives of some patients, or improve the quality of remaining life.

In most cases, surgeons open the skull through a craniotomy to best access the tumor site. This is done frequently with image guidance and at times using intra-operative mapping techniques to determine the locations of motor, sensory and speech/language cortex.

Some time after surgery, when the wound is healed, radiation therapy can begin. The goal of radiation therapy is to selectively kill tumor cells while leaving normal brain tissue unharmed. In standard external beam radiation therapy, multiple sessions of standard-dose "fractions" of radiation are delivered to the tumor site as well as a margin in order to treat the zone of infiltrating tumor cells. Each treatment induces damage to both healthy and normal tissue. By the time the next treatment is given, most of the normal cells have repaired the damage, but the tumor tissue has not. This process is repeated for a total of 10 to 30 treatments, depending on the type of tumor. This additional treatment provides most patients with improved outcomes and longer survival rates compared to surgery alone or the best supportive care.

Radiosurgery is a treatment method that uses specialized radiation delivery systems to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be used in select cases for tumor recurrence, often using additional information derived from MRS (magnetic resonance spectroscopy) or PET scans (positron emission tomography).

Patients undergoing chemotherapy are administered special drugs designed to kill tumor cells. Chemotherapy with the drug temozolomide is the current standard of treatment for GBM. The drug is administered every day during radiation therapy and then in 6-8 cycles for 5 days at higher doses once radiation is completed. While the aim of chemotherapy is to produce long-term tumor control, it does so in only about 20 percent of patients. The decision to prescribe other forms of chemotherapy for tumor recurrence is based on a patient’s overall health, type of tumor, and extent of the cancer. Before considering chemotherapy, you should discuss it with your oncologist/neuro-oncologist.

Because traditional treatment modalities are unlikely to result in a prolonged remission of GBM tumors, researchers are presently investigating several innovative treatment modalities in clinical trials. A number of these treatments are being made available on an investigational basis at centers specializing in brain tumor therapies. These include gene therapy, highly focused radiation therapy, immunotherapy and chemotherapies utilized in conjunction with vaccines. One of the more promising vaccine and chemotherapy studies yielded an average time for recurrence of the tumor after treatment of 16.6 months; as compared to the previous 6-month average recurrence. However, it is important to note that while some of these investigational treatments show promise, the most effective therapies introduced over the past three decades have improved median survival of GBM patients by an average of only three months.

Copyright, the American Association of Neurological Surgeons, June 2008.

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