Glioblastoma

Glioblastoma symptoms may be generalized or specific to the location of the tumor. They can be subtle. Some common symptoms include:

• Headaches (persistent, increasing in intensity over time, may wake a person up at night)
• Vomiting
• Seizures (new onset)
• Memory problems
• Blurred vision
• Mood disturbances
• Changes in personality
• Fatigue
• Balance problems
   

Symptoms specific to the location of the glioblastoma are called focal neurologic deficits. Some examples of focal neurologic deficits are:

• Numbness, weakness, or involuntary movements of a specific part of the body
• Loss of coordination or fine motor control
• A problem understanding or producing words (aphasia)
• Loss of peripheral vision
• Shaking movements of one extremity (a focal seizure)
• Abnormal smell or taste sensations

Most glioblastomas are sporadic tumors that arise in people without known risk factors.

• Exposure to Ionizing Radiation. People who have had radiation therapy (ionizing radiation) to treat cancer have an increased risk of developing glioblastoma, especially those who received radiation treatment to their head and neck during childhood.
  
  Other forms of radiation, such as those from power lines, cellular phones, and microwave ovens, have not been shown to increase the risk of glioma.
  
  
• Family history. Glioblastoma rarely runs in families, but some diagnosed cases may have a genetic component.
  
  Some rare hereditary cancer syndromes, like Li-Fraumeni syndrome and neurofibromatosis, are characterized by the early onset of multiple tumors, including glioblastoma.
  
  Some inherited gene variants have been associated with a small increased risk of glioblastoma. Inheriting one of these "risk variants" does not necessarily mean the person will develop glioblastoma. Additional mutations are still required to lead to tumor formation.

Since the symptoms caused by astrocytoma can be present with other illnesses, a careful evaluation is necessary to make a diagnosis.

• Neurological Examination. A thorough evaluation of the nervous system includes assessment of: mental status (awareness, memory), cranial nerves (nerves responsible for eye movement, taste, facial expressions), speech (speaking and understanding), muscle strength and grip, sensory function (ability to feel light touch, vibrations, temperature changes), balance and coordination, and reflexes.
  
  
• Imaging.  Magnetic resonance imaging (MRI) is often taken before and after the administration of intravenous contrast to visualize the tumor. Other imaging tests may be used to evaluate the tumor or help plan treatment, including computerized tomography (CT) scan, positron emission tomography (PET), functional MRI, perfusion MRI, and magnetic resonance spectroscopy.
  
  
• Surgery. When the history, neurological examination, and images are concerning for an astrocytoma, the next step is to obtain diagnostic tissue. A tissue sample is required to establish the diagnosis and accurately classify the glioma. Tissue can be obtained during open surgery or by stereotactic biopsy.   Both procedures are performed in the operating room, usually under general anesthesia.
  
  Procedure selection is based on suspected tumor subtype, grade, location, and operability. In general, surgical strategies are to remove as much tumor as possible safely but if the tumor involves eloquent brain, a biopsy is usually performed.
  
  A pathologist analyzes the tissue under a microscope to provide a preliminary diagnosis. Subsequent analysis involves special tissue staining techniques and molecular analysis and take days to weeks to finalize the diagnosis.

Histology

Pathologists use a microscope and special stains to identify the type of glial cell in the tumor sample.

Astrocytes are star-shaped glial cells that help maintain the appropriate chemical environment for neuron signaling. They usually give rise to glioblastoma.

Pathologists also look for signs of tumor malignancy (aggressiveness), such as:

• Irregular cellular appearance
• Cells actively multiplying
• Formation of new blood vessels
• Necrosis (dead tissue)
   

Molecular Analysis

The presence of specific genetic markers (mutations) has been shown to be a reliable predictor of tumor behavior and treatment response.

Examples of genetic markers relevant in categorizing glioblastoma include:

• Isocitrate dehydrogenase (IDH) mutation – When the mutation is present (IDH-mutant), the tumor is not as aggressive, and patients tend to live longer. Glioblastoma tumors do not possess the favorable IDH-mutant biomarker. They are categorized as IDH-wildtype, which means they are aggressive tumors, relatively resistant to treatment, and have a correspondingly poor prognosis.
• Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter – MGMT methylation status predicts a favorable outcome in patients who are exposed to certain kinds of chemotherapy.
• Genetic changes/mutations.  Tumors are also assessed for genetic changes in genes such as P53 and others.
   

Genetic markers provide clues about the tumor and allow physicians to individualize the treatment plan.

Grading

Pathologists also consider the cellular appearance and presence of genetic markers to assign a grade to the tumor. Grading is a prediction of how the cancer would behave without treatment. In glioma, a grade is assigned within a particular subtype and can range from 1 to 4. Malignancy increases with a higher grade. Glioblastoma tumors are always categorized as grade 4.

Surgical resection, radiation therapy, and chemotherapy are the primary treatment options.  In certain situations, aggressive resection can help change the natural history of this tumor.  The location, size, and subtype of glioblastoma determine which combination of treatments is optimal.

Learn more about treatment options >

Symptom Management

Treatment also includes managing symptoms caused by the glioblastoma.

People who experience seizures are treated with an antiseizure drug, such as levetiracetam. Tumor-induced seizures can be challenging to treat, and surgical resection may be able to reduce seizure activity.

Glucocorticoids (steroids) can improve headaches and neurologic deficits caused by cerebral edema. Dexamethasone is frequently prescribed for this purpose but is associated with significant side effects and may shorten survival. Glucocorticoids are used at the lowest effective dose and, ideally, only until other treatments are planned.

Palliative medicine is a medical specialty focused on relieving the symptoms that people with serious illnesses endure. The goal of palliative therapy is to reduce the suffering caused by cancer and ensure the quality of life is maximized during cancer treatment. 

Treatment Innovations

Treatment options for astrocytoma have expanded in recent years. Some recent treatment advances include:

• Tumor treating electrical fields (Optune): A device worn on the scalp delivers alternating electrical fields to prevent the growth and division of cancer cells.
• Convention-enhanced delivery – Chemotherapy is slowly and continuously delivered to the tumor via a pump.
• Implanted chemotherapy wafer therapy (Gliadel) – Chemotherapy is released directly into the remaining tumor from a disc embedded during surgical resection.
• Nanoparticle therapy – Special particles allow chemotherapy drugs to cross the blood-brain barrier and improve access to the tumor.
   

Learn more about treatment innovations at Stanford >

Ongoing research is needed to improve our understanding of brain tumors and develop more effective therapies. Some treatments currently being studied are:

• Immunotherapies. Immunotherapy is a type of treatment that uses the patient's immune system to fight cancer. Some experimental immunotherapies for brain tumors include checkpoint inhibitors, CAR T-cell therapy, and vaccines.
• Molecular targeted therapies. Targeted therapy is a type of treatment that targets specific molecules or pathways involved in cancer growth and survival. Some experimental targeted therapies for brain tumors include drugs that target mutations in the IDH1 and IDH2 genes.
  
  

Patients may participate in clinical trials to access new treatments under investigation. Please check with your physician to see if you are eligible for a clinical trial.

 Learn more about our open clinical trials >