All About Adult Gliomas

Elizabeth N. Kuhn, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 16 de abril del 2014

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What is a glioma?

A glioma is a type of brain tumor that originates in the brain, a so-called "primary brain tumor." This is different than a brain tumor that has spread from another area of the body, which is called a metastasis.

Gliomas are tumors that arise from "glial" cells. While neurons are the cells that carry signals, glial cells are the support cells in the brain that help keep neurons in place and functioning well. There are many more glial cells than neurons, and glial cells come in several types, including astrocytes, oligodendrocytes and ependymal cells. All types of glial cells arise from a common brain stem cell (stem cells are a type of cell that can turn into many different types of cells). Gliomas form when these immature stem cells mutate and grow out of control.

Am I at risk for a glioma?

There are few known risk factors for gliomas. Prior exposure to ionizing radiation, either to treat a medical condition (for example, a childhood cancer) or as a result of nuclear weapon exposure, increases glioma risk. There are also several genetic conditions that predispose individuals to developing multiple types of cancer, including gliomas. Individuals with these genetic syndromes often have family members with a history of multiple cancers. Some of these genetic syndromes include Li-Fraumeni Syndrome, melanoma-astrocytoma syndrome, neurofibromatosis (types 1 and 2), Turcot's syndrome (types 1 and 2), and BRCA syndrome. If you have been diagnosed with multiple cancer types, or multiple cancer types run in your family, consider asking your doctor if you could be at risk for having a genetic syndrome.

Despite much press, cell phone use has not been shown to increase the risk of developing a brain tumor. Similarly, there is no conclusive evidence to suggest that aspartame (a sugar substitute), power lines, or industrial chemicals increase your risk of developing a brain tumor.

What are the signs and symptoms of a glioma?

The signs and symptoms of a glioma are similar to those for all brain tumors. The most common symptoms include:

  • Headache
  • Nausea and/or vomiting
  • Confusion
  • Seizures
  • Memory loss
  • Vision loss or blurred/double vision
  • Difficulty with speech or language
  • One-sided weakness
  • Difficulty with walking or balance
  • Personality changes

These symptoms usually come on gradually over a period of days to months. Depending on what part of the brain the glioma is in, the symptoms may vary. Patients with brain tumors are also at increased risk of developing blood clots in the leg (deep vein thrombosis, DVT), lung (pulmonary embolism, PE), or brain (stroke). Unfortunately, the symptoms of a brain tumor are quite general and can also be caused by a number of other, non-cancerous, conditions. If you have the symptoms above, you need to be evaluated by your healthcare provider.

How are gliomas diagnosed?

When a patient has the signs and symptoms above, MRI (magnetic resonance imaging) with contrast of the brain is used to evaluate whether a brain tumor is present and characterize the tumor. MRI has largely replaced CT scans because MRI provides more detailed images of the brain and brain tumor and MRI does not use radiation. However, CT scans must be used in patients who cannot obtain an MRI (eg. patients with metal objects in their body). Learn more about the difference between MRI and CT. While imaging with MRI or CT can suggest a brain tumor, the type of brain tumor cannot be known with certainty without looking at a piece of the tumor under a microscope. This is usually done by a pathologist, a type of doctor who specializes in examining tissues under a microscope and making a diagnosis. A biopsy or surgical removal of the tumor, therefore, is required to conclusively diagnose a brain tumor as a glioma.

How are gliomas classified and staged?

Gliomas are classified as either low-grade or high-grade, based on their appearance under a microscope. Low-grade gliomas typically occur when patients are in their 20s-30s, while high-grade gliomas are more common above 50 years old. Gliomas are also classified based on the type of cells from which it originates. For example, a tumor composed of astrocytes is called an astrocytoma, a tumor composed of oligodendrocytes is called an oligodendroglioma, and a tumor composed of ependymal cells is called an ependymoma. A mixed glioma (also called an oligoastrocytoma) is a tumor composed of a mixture of these cells.

The glioma's grade is based on the World Health Organization classification, and considers the cell type that makes up the tumor and how aggressive it looks under the microscope. The term "anaplastic" is used to describe aggressive tumors, which may grow more rapidly, invade surrounding brain, and have a tendency to return after treatment. Gliomas are graded on a scale from I-IV, with grade I tumors growing the slowest and grade IV tumors carrying the worst prognosis. Grade I gliomas, called pilocytic astrocytomas, are rarely seen in adults, and thus excluded from the scope of this article. (More information about pediatric brain tumors).

Type of Brain Tumor World Health Organization Grade
Low-grade gliomas
  • Astrocytoma
II
  • Oligodendroglioma
II
  • Oligoastrocytoma (mixed glioma)
II
High-grade gliomas
  • Anaplastic astrocytoma
III
  • Anaplastic oligodendroglioma
III
  • Anaplastic oligoastrocytoma (mixed glioma)
III
  • Anaplastic ependymoma
III
  • Glioblastoma
IV

What are the treatments for gliomas?

Surgery

There are 3 main goals of surgery: 1) establish a diagnosis of glioma and determine the grade; 2) improve symptoms by decreasing the size of the glioma; 3) achieve cure (when possible) or, when cure by surgery alone is not possible, decrease the tumor size to increase the effectiveness of other treatments. Most symptoms from gliomas are due to either increased pressure in the brain or compression of normal brain tissue. By removing some (if not all) of the tumor, pressure and compression are decreased, improving symptoms.

You may wonder what determines whether a tumor can be removed completely by surgery. The real estate rule "location, location, location" is also the guiding principle in brain tumor surgery. If a tumor is located in the speech and language or motor center, for example, complete removal of the tumor may not be possible without damaging speech, language, or movement. In other areas of the brain, it may be safe to remove the entire brain tumor. Consult with a neurosurgeon if you have questions about whether or not a tumor can be safely removed in its entirety.

Chemotherapy

Chemotherapy is the use of medicines or drugs that are designed to kill cancer cells. Chemotherapy can either be a pill that you take by mouth or a liquid that is given through an IV into the bloodstream (intravenous). For chemotherapy to be able to kill glioma cells, it must be able to pass from the bloodstream into the brain. The brain is protected by the blood-brain-barrier, a specialized defense that prevents many toxins and chemicals (including some medicines) from entering and damaging the brain. Only certain chemotherapy medicines are able to cross the blood-brain-barrier.

The most commonly used chemotherapy agents for glioma are temozolomide (Temodar) and bevacizumab (Avastin). Temozolomide is a pill taken by mouth; its anti-cancer effect is through the process of alkylation. Alkylation causes damage to the DNA of a tumor cell preventing it from growing and dividing, causing the cancer cell to die. The most common side effects of temozolomide are low blood counts, nausea and vomiting, loss of appetite, fatigue, and hair loss. Bevacizumab is given through an IV, directly into the bloodstream. It works by preventing the growth of blood vessels, essentially killing a tumor by cutting off its blood supply. The most common side effects of bevacizumab are bleeding, high blood pressure, poor wound healing, and kidney damage. Ask your oncologist about which chemotherapy (if any) may be right for you.

Radiation Therapy

Radiation therapy (radiotherapy) is commonly used to treat many different types of brain tumors. Radiation therapy is a "focal" therapy, meaning that the only portion of the brain treated is the region where the radiation is aimed. Gliomas are treated with fractionated radiation, which is the type of radiation therapy where a small dose of radiation is given to the area of the brain tumor 5 days a week, for several weeks. Over the treatment period, the amount of radiation to the tumor accumulates and causes the tumor cells to die. A more detailed overview of radiation therapy can be found here, along with a pictorial description of the process. The most common side effects of radiation to the brain are fatigue, hair loss, and memory loss. Other side effects depend on the location of the tumor. The fatigue and hair loss occur during the radiation treatment and last for about 4-6 weeks after radiation treatment is over. Memory loss develops over the years after radiation treatment, though you may notice some changes right away. It is often said that radiation to the brain is "like aging, but faster," meaning that the cognitive changes that normally happen with aging happen much sooner if you have had radiation. Ask your radiation oncologist about the details of your treatment what side effects you may be at risk for.

Other Treatments

Steroids, like prednisone or dexamethasone, may be a part of your glioma treatment. Steroids are anti-inflammatory medications that are used to decrease swelling in the brain that may develop from the tumor itself or its treatment. Some common side effects of steroids are infection, stomach ulcers or bleeding, weight gain, difficulty sleeping, and mood changes.

Another category of treatments used for gliomas (especially high-grade and recurrent glioma) is the so-called "implants." Implants are typically small "seeds" or "wafers" which contain either chemotherapy or radiation. Implants are designed to bypass the blood-brain-barrier, by delivering treatment directly to the site of the tumor. Chemotherapy wafer implants (called Gliadel®) are small gel wafers containing the chemotherapy agent carmustine (BCNU). During surgery, a neurosurgeon places up to 8 wafers in the area where the tumor was (the so-called "tumor cavity"). Over the subsequent few days, the wafers release chemotherapy directly into the site of the tumor. The wafers dissolve completely in 2-3 weeks. 

Brachytherapy is "internal" beam radiotherapy, meaning that the radiation source is inside the body, very close to the tumor. In the case of gliomas, brachytherapy can come in several forms, most commonly iodine-125 (125I) seeds and GliaSite®. GliaSite® is a radiation delivery system used for gliomas. During brain surgery, a neurosurgeon places a small balloon into the tumor cavity. A few weeks after the balloon is implanted, it is filled with liquid radiation, which delivers radiation to the surrounding tumor for a period of 3-6 days. After that time, the balloon and liquid are removed from the brain. Iodine-125 seeds are similar to GliaSite®; they too are placed by a neurosurgeon into the tumor cavity during brain surgery. The seeds also deliver radiation to the surrounding tumor, but, unlike GliaSite®, the iodine-125 seeds do not need to be removed.

Which treatment(s) is right for me?

Treatment depends on whether the glioma is low-grade or high-grade. There are different treatments used for recurrent high-grade gliomas, those gliomas which return despite treatment.

Low-grade glioma

While low-grade gliomas carry a better prognosis than high-grade gliomas, they are not benign. If left untreated, low-grade gliomas will progress to become high-grade gliomas. The prognosis varies considerably based on the type of tumor; patients with astrocytoma live on average 5-10 years after diagnosis while patients with oligodendroglioma can live 10-15 years after diagnosis. The prognosis is also better for patients who are younger than 40 years old and who have smaller tumors before surgery (less than 5-6 cm).

There is no standard treatment for low-grade gliomas, though surgery to remove as much of the tumor as possible is recommended for most patients. If a young patient (less than 40 years old) has complete removal of their tumor, no additional treatment is generally needed. If a patient is older than 40 years or has incomplete surgical removal of their tumor, radiation is often recommended. Often, clinicians attempt to delay radiotherapy for as long as possible because patients with low-grade gliomas tend to be younger. Delaying (or avoiding) radiotherapy attempts to spare patients the memory loss and cognitive troubles that often develop after radiation to the brain. Chemotherapy is sometimes recommended for oligodendrogliomas, which tend to respond better to chemotherapy than astrocytomas. 

High-grade glioma

The most common types of high-grade glioma are glioblastoma and anaplastic astrocytoma. High-grade gliomas cannot be cured and carry a poor prognosis; the median survival for glioblastoma is 14-18 months and for anaplastic astrocytoma is 2-2.5 years. Quality of life issues are of paramount importance in the treatment of patients with high-grade glioma. Some quality of life issues to consider are fatigue, overall health, cognitive function, social function, emotional function, financial burden, future uncertainty, and insomnia. Prognosis and palliative care or hospice choices, along with end-of-life preferences, are discussed very early on in the course of a patient's illness. Measuring quality of life is important to fully understand the impact of a treatment on the disease; while the goal is improved survival, it must not be at the expense of quality of life.

A pivotal study (known as the Stupp trial) in treatment of glioblastoma found that combination treatment with temozolomide and radiation therapy significantly improved survival. These researchers found a group of patients who responded especially well to temozolomide – these patients all had a similar mutation in their tumors, causing the MGMT gene to be turned off. The MGMT gene is responsible for repairing DNA when it becomes damaged. When this gene is turned off, DNA damage caused by temozolomide (through the process of alkylation) cannot be repaired, leading to cell death. The Stupp trial established the standard treatment for glioblastoma. While a standard treatment for anaplastic astrocytoma has not been so clearly established from research studies, most doctors treat anaplastic astrocytomas like glioblastomas.

Based on the Stupp trial, high-grade gliomas are first treated with surgery, removing as much tumor as is safe. After surgery, the standard treatment is a combination of fractionated radiotherapy for six weeks and temozolomide (Temodar). Temozolomide is given until the tumor begins to grow again (called tumor progression). In the setting of tumor progression, chemotherapy with bevacizumab (Avastin) is commonly used, though other chemotherapy drugs, including experimental treatments, may be tried.

Recurrent High-Grade Glioma

Unfortunately, high-grade gliomas are often resistant to treatment or return after treatment. In fact, in excess of 90% of patients with glioblastoma will experience at least one recurrence. Patients whose tumors do not improve with radiation and temozolomide are candidates for participation in a clinical trial. Treatment options for recurrent high-grade glioma include surgery and chemotherapy. Survival after re-resection (surgery) is typically 4-5 months. Some patients are offered re-resection along with chemotherapy wafers (Gliadel) or radioactive implants (eg. GliaSite). Chemotherapy options include bevacizumab (Avastin), irinotecan (Camptosar), nitrosoureas (eg. carmustine, lomustine) or platinum-based agents (eg. cisplatin, carboplatin, oxaliplatin).

Clinical Trials

Glioma, especially high-grade glioma, is an area of active research and numerous clinical trials. Currently, clinical trials are investigating new therapeutic agents, new combinations of existing treatments, and different sequencing or timing of treatments. Treatments currently in clinical trials include novel chemotherapy agents, vaccine therapy, and specialized diets. You can learn more about ongoing clinical trials and find those that may be right for you using the OncoLink Clinical Trials Matching Service or online at clinicaltrials.gov.

References and Additional Reading

American Brain Tumor Association

National Brain Tumor Society

Darakchiev BJ, Albright RE, Breneman JC, Warnick RE. Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme. J Neurosurg 2008; 108:236 – 242.

Dorsey JF, Hollander AB, Alonso-Basanta M, Macyszyn L, Bohman L, Judy KD, Maity A, Lee JYK, Lustig RA, Phillips PC, Pruitt AA. Chapter 66. Cancers of the Central Nervous System. Niederhuber: Abeloff's Clinical Oncology, 5th edition. Philadelphia, PA: Churchill Livingstone; 2008.

Fernandes A. MGMT promoter methylation as predictive biomarker for response to radiotherapy versus chemotherapy in malignant astrocytomas in the elderly: the NOA-08 trial. OncoLink Reports from ASCO 2012.

Hegi ME, Diserens AC, Gorlia T, et?al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997.

Kyritsis AP, Bondy ML, Rao JS, Sioka C. Inherited predisposition to glioma. Neuro-oncology. 2010, 12(1):104-113.

Merrell R. Brain Tumors. Section 10: The Nervous System. Bope and Kellerman: Conn's Current Therapy 2014, 1st edition. Philadelphia, PA: Elsevier Saunders; 2014.

Stupp R, Mason WP, Vanden Bent MJ, et?al. Effects of radiation therapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10(5):459–466.

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