Glioblastoma

The most commonly diagnosed primary malignant brain tumor of adults is the glioblastoma multiforme (GBM).

What is a Glioblastoma?

The glioblastoma multiforme is graded by the World Health Organization as a grade IV astrocyotoma (the highest grading designation). This classification also includes the grade IV variants: giant cell glioblastoma and gliosarcoma.

The characteristic features of a glioblastoma multiforme is that is grows fast and invades into adjacent tissue. Under the microscope one can find astrocytic cells, mitotic figures (dividing cells), new blood vessel growth (angiogenesis) and dead cells called necrosis. A Glioblastoma multiforme can occur at any age but is typically seen in people between 45 and 70 years old. These brain tumors are found most commonly in the subcortical white matter of the frontal lobes, and the tumor cells can cross from one side of the brain to the other (usually in a structure called the corpus callosum). Rarely does the tumor affect sites outside of the brain. Active research is under way to help identify the cause of these tumors. Less than five percent of all primary brain tumors such as the glioblastoma multiforme have any known hereditary factors.

Symptoms & Diagnosis

The most common signs and symptoms of glioblastoma multiforme are seizures, progressive headaches, or progressive loss of brain function (such as speech, strength, memory, etc.). Computerized Axial Tomography (CT) scans and Magnetic Resonance Imaging (MRI) scans with and without contrast typically show an enhancing abnormality that "lights-up" after contrast is given. Edema or swelling is also commonly seen on these studies. Magnetic Resonance Spectroscopy (MRS), Magnetic Resonance Cerebral Blood Volume (MRCBV) or Positron Emission Tomography (PET) may give insights into the metabolism of the area of abnormality.

Treatment Options

For a glioblastoma multiforme, patients may undergo a surgical procedure called a craniotomy for diagnostic and or debulking (removing as much tumor as possible) purposes. Since these tumors infiltrate into the brain to variable distances, not all the malignant cells can be removed; thus, additional treatment is most commonly recommended. A pathologist who will identify the tumor type examines tissue taken at the time of surgery.

Glioblastoma multiforme represents a heterogeneous cell population, which means that certain cells may be more resistant to treatment than others. This is what makes a glioblastoma multiforme difficult to treat. The most common treatment performed worldwide after surgery is radiation therapy, so patients need to be seen by a radiation oncologist. Radiation typically takes place five days a week over a six-week period. The radiation first is given to a specified area of the brain to help reach the tumor cells that are further away. A radiation "boost" then is given closer to the area of the glioblastoma bulk, where more tumor cells are located.

Chemotherapy has been used for many years to treat these brain tumors and has been given before, during or after radiation therapy. Historically BCNU, CCNU and Procarbazine have been used. More recently Temodar has been used and shown to improve prognosis when given early in the disease. Chemotherapy also can be placed locally at the time of surgery using a Gliadel wafer, which is impregnated with BCNU and placed around the surgical cavity during tumor resection.

New Treatments

At Cleveland Clinic, we have access to alternative radiation delivery methods including stereotactic radiotherapy (Gamma Knife), Intensity Modulated Radiotherapy (IMRT ) and Novalis. Radiation can also be given using implanted seeds (I131) or by placing liquid radiation into a balloon (GliaSite), which is placed into the surgical cavity after tumor removal. Drugs called Radiation Sensitizers given at the time of radiation also are used in a clinical research setting as part of a clinical trial.

Many clinical trials are under way around the country investigating novel drugs for the treatment of these brain tumors. Cleveland Clinic is a member of various consortiums investigating some of these new drugs. We offer clinical trials through ABTC, (American Brain Tumor Consortium), RTOG (Radiation Therapy Oncology Group), SWOG (Southwest Oncology Group), and NABTT (New Approaches to Brain Tumor Therapy - a National Cancer Center Consortium). We also run a number of industry-sponsored clinical trials to study new and novel drugs such as immunotoxins delivered by convection enhanced delivery - a process where the drug is slowly, continuously pumped through the brain over several days. The Tarceva Trial, for example, is measuring the effect of an epidermal growth factor receptor (EGFR) antagonist, because EGFR has been shown to be overexpressed in some GBMs.

A recurrent glioblastoma multiforme can be treated in a fashion similar to upfront GBMs. Certain clinical trials are used in the upfront setting and other trials are under way for the treatment of recurrent tumors. Active clinical trials also are ongoing around the country using gene therapy, monoclonal antibodies and various biological modifiers.

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