Brain and nerves- Brain tumors
Patient information: Primary low-grade glioma in adults
Author
Lawrence D Recht, MD
Section Editors
Patrick Y Wen, MD
Jay S Loeffler, MD
Deputy Editor
Michael E Ross, MD
Disclosures
LOW GRADE GLIOMA OVERVIEW — Primary brain tumors are cancers that originate in the brain. These tumors are very different from secondary brain tumors, which originally developed elsewhere in the body and spread (metastasized) to the brain.
Primary brain tumors develop from glial cells. Glial cells provide the structural backbone of the brain and support the function of the neurons (nerve cells), which are responsible for thought, sensation, muscle control, and coordination.
In this article, we will discuss the symptoms, diagnosis and treatment of low-grade gliomas, an important category of primary brain tumors. For information about high-grade gliomas, (see “Patient information: High-grade glioma in adults”). More detailed information about low-grade gliomas is available by subscription. (See “Management of low-grade glioma”.)
CLASSIFICATION OF PRIMARY BRAIN TUMORS
Low-grade versus high-grade gliomas — Primary brain tumors are tumors that classified according to their appearance under the microscope. Gliomas are classified into four grades (I, II, III, and IV), and the treatment and prognosis depend upon the tumor grade [1]. Grade I or II tumors are termed low-grade gliomas.
Types of low-grade glioma — Low-grade gliomas are subdivided based upon the microscopic appearance of the tumor. The more common subtypes are:
Diffuse astrocytomas — Diffuse astrocytomas are the most common low-grade glioma. They are usually diagnosed in individuals in their late thirties.
Pilocytic astrocytomas — These tumors occur almost exclusively in people who are younger than 25 years of age. It is important to distinguish pilocytic astrocytomas from other low-grade gliomas because these tumors tend to progress very slowly.
Oligodendrogliomas — Oligodendrogliomas can be slow-growing tumors.
Gangliogliomas — These tumors have features of both gliomas and of tumors arising from neurons, the other type of cell within the brain. These tumors tend to grow very slowly.
Mixed gliomas — Some low-grade gliomas consist of mixtures of various tumor subtypes (eg, diffuse astrocytoma and oligodendroglioma). These tend to behave similarly to diffuse astrocytomas.
LOW GRADE GLIOMA SYMPTOMS — Low-grade gliomas do not spread outside the brain, but instead grow into the normal brain tissue, creating symptoms as the tumor grows locally. This can disrupt connections between normal brain cells and can also create pressure on the nearby brain. The brain cannot expand when there is a tumor growing within it since it is confined within the skull. As a result, even a relatively small, slow-growing tumor can cause severe brain problems, particularly if the tumor is in a critical area of the brain.
In many people, a seizure is the first sign of a low-grade glioma. Seizures, which also occur as a result of other conditions, are caused by disorganized electrical activity in the brain. Seizures can cause a loss of consciousness (passing out), involuntary movements (jerking or fits), and/or loss of muscle control throughout the body.
Seizures can be controlled with medications. In people with a low-grade glioma who are diagnosed after a seizure, there may be no other signs of the tumor once the seizure is controlled with medication.
Other people have symptoms due to swelling around the tumor (called cerebral edema) or blockage of the normal cerebrospinal fluid that circulates within the brain (called obstructive hydrocephalus). In either case, symptoms can include headache, nausea and vomiting, diminished consciousness, weakness or numbness, and loss of mental sharpness or difficulty concentrating. The area of the brain affected by the tumor and/or the swelling determine the specific symptoms.
LOW GRADE GLIOMA TESTS — All of the symptoms described above, including seizures, can be caused by neurologic illnesses other than tumors and by non-neurologic diseases (eg, infections, endocrine disorders). A clinician will need to do a careful history and physical examination, as well as basic laboratory and x-ray tests, to determine the cause of symptoms. The presence of a brain tumor is often established by x-ray or imaging studies.
Imaging studies — If a brain tumor is suspected, the physician will want to obtain an imaging scan of the brain. This is done using either magnetic resonance imaging (also known as an MRI) or computed tomography (also known as CT or CAT scan). A major difference between an MRI and a CT scan is that the MRI uses a magnet to image the brain, while CT uses x-rays. Both give a detailed image of the brain’s structure, and both can usually show the presence and location of a tumor.
CT scans are generally more available and less expensive than MRI scans, so a head CT is often the first test that is ordered. However, the MRI provides much more useful information when a brain tumor is suspected and may be recommended after a tumor is confirmed.
Sometimes, the findings on the brain CT or MRI are sufficiently clear that the diagnosis of a low-grade glioma is fairly certain. In such cases, a biopsy may not be necessary. However, in most cases, a biopsy is recommended to establish the type of tumor that is present (see ‘Biopsy’ below).
It is important to characterize a brain tumor as a low-grade glioma, high-grade glioma, or a different type of tumor altogether. A non-invasive x-ray test that may help in this distinction is a positron-emission tomography, or PET scan. During this test, a radioactive glucose (a sugar) is injected into the bloodstream, which then circulates to the brain. Differences in how the brain absorbs the glucose often help to identify a tumor, and may help to distinguish between a low-grade glioma, high-grade glioma, and other brain tumors.
Biopsy — A biopsy is usually required to establish the diagnosis and subtype of a brain tumor and plan appropriate treatment. Biopsy involves the removal of a small amount of tissue from the brain so that it can be examined under a microscope
A brain biopsy may be done in conjunction with surgery to remove the tumor. Alternatively, a small sample may be removed from the tumor by stereotactic needle biopsy, which involves the insertion of a needle through the skull into the precise area of the tumor, using x-ray guidance. Although both surgical biopsy and stereotactic needle biopsy are usually safe, brain damage is a potential complication.
A biopsy may be delayed until symptoms worsen or there is evidence of tumor growth or a change (on imaging tests) that suggests that the tumor is becoming more aggressive. The decision regarding the optimal timing of a biopsy requires the physician and patient to carefully weigh the risks of the biopsy against the benefit of knowing the specific type of tumor that is present.
LOW GRADE GLIOMA TREATMENT — Treatment of a low-grade glioma must consider the best way to manage symptoms and remove or reduce the tumor. The optimal treatment of low grade-glioma (particularly the timing of treatment) is controversial, and treatment decisions must balance the benefits of therapy against the potential for treatment-related complications.
Symptom management — Seizures, cerebral edema (swelling in the brain around the tumor), and obstructive hydrocephalus (increased pressure within the brain due to blockage of the flow of cerebrospinal fluid within the brain) can all result in serious symptoms. Each of these requires a different therapeutic approach:
The same medications used to treat epilepsy are usually successful in controlling seizures associated with brain tumors. However, seizures may be more difficult to control in people with brain tumors, particularly low-grade gliomas. If medications are not effective, surgery to remove part of the tumor may be recommended in an attempt to reduce seizure activity.
Cerebral edema usually can be treated successfully with steroids; the most commonly used steroid is dexamethasone (Decadron). Dexamethasone use can be temporary if specific treatment of the tumor is planned, and the treatment is expected to decrease edema. Dexamethasone may be used for a more prolonged period of time if treatment is not currently planned. Dexamethasone may be particularly useful in the late phases of the illness, such as if the tumor recurs and there is no other way to control cerebral edema.
One of the problems with long-term use of dexamethasone (particularly high doses) is the potential for side effects (eg, ulcers, bleeding from the gastrointestinal tract, behavioral changes, thinning of the skin, loss of bone strength, high blood sugar). Thus, the dose of dexamethasone is tapered to achieve the lowest dose that effectively controls symptoms, yet minimize long-term complications.
Obstructive hydrocephalus may require surgery to bypass the blockage and lower the pressure within the brain.
Treatment of the tumor — Surgery, radiation therapy, and chemotherapy may be used to treat a low-grade glioma, either separately or in combination. (See “Management of low-grade glioma”.)
Surgery — The objective of surgery is to remove as much of the tumor as possible while minimizing damage to the normal brain. While people with juvenile pilocytic astrocytomas do particularly well after removal of their tumors, the benefit of surgery on survival with other types of low-grade glioma is less clear.
Low-grade gliomas grow into normal brain, and there is often no distinct boundary between the tumor and normal brain. As a result, efforts to remove all tumor cells inevitably remove some of the normal brain and can leave behind tumor cells. The remaining glioma cells continue to grow, eventually causing additional damage to the remaining normal brain, and a recurrence of symptoms. Thus, surgery, even when extensive, rarely results in cure of adults with low-grade glioma.
Whether or not all patients should have surgery after initial diagnosis is an area of controversy:
Some physicians recommend removal of as much tumor as possible in all patients as soon as the diagnosis of a brain tumor is made. This recommendation is based upon studies suggesting that patients who have immediate surgery survive longer, possibly because the tumor is less likely to change into a more aggressive form.
Other physicians recommend that carefully selected patients initially be observed without therapy, until the tumor grows or symptoms worsen despite medical therapy. The rationale behind this approach is that low-grade gliomas may progress very slowly, surgery can create more symptoms than are caused by the tumor, and surgery done later may be equally effective in prolonging survival.
The physician and patient must try to balance the benefits of removing tumor versus the potential for surgery to damage to normal brain. The amount of tissue removed and whether surgery is possible are influenced heavily by the location of the tumor within the brain:
If the tumor is in an area of the brain controlling one or more critical functions (eg, swallowing), surgery may result in severe damage. In this setting, the physician may recommend against surgery or recommend limiting the amount of tumor removed during surgery.
If the tumor is in a less critical area of the brain, the physician may recommend trying to remove as much of the tumor as possible.
Other accepted reasons for surgery include increased pressure within the brain, symptoms caused by the tumor or a bleed (hemorrhage) into the tumor, or seizures that are unresponsive to medications.
Radiation therapy — Radiation therapy (also called radiotherapy or x-ray therapy) uses high energy x-rays that are carefully aimed at the area of the brain affected by the tumor. Radiation therapy is generally given in a series of treatments over several weeks. The total radiation dose, which is based upon the number of treatments and the amount of radiation administered per treatment, is carefully calculated to maximize the killing of tumor cells and minimize damage to the normal brain.
In people with low-grade gliomas, radiation therapy may be recommended in three circumstances:
Radiation can be given after surgery, with the objective of eradicating tumor cells that were not removed at the time of surgery. The effectiveness of immediate radiation therapy after surgery is unclear. Because the benefit is uncertain and radiation has the potential for long-term neurologic side effects, postoperative radiation is often not recommended (see below).
Radiation therapy may be the preferred treatment when a low-grade glioma has been diagnosed in a critical area of the brain that cannot be surgically removed, and therapy is felt to be necessary.
Radiotherapy can be used later in the course of the illness, when there is evidence that the tumor has recurred and is causing symptoms. The use of radiation therapy at this time will depend upon how much radiation was given previously, since radiation cannot usually be given in full doses to the same area of the brain more than once.
A major problem with radiation therapy is treatment-related side effects. Radiation kills both tumor cells and normal cells, although tumor cells are somewhat more sensitive to the effects of radiation. Nevertheless, radiation therapy cannot kill all tumor cells without damaging adjacent normal brain, and this results in treatment-related side effects.
The most common side effect is damage to the surrounding normal brain cells, resulting in gradually worsening impairment of mental sharpness and ability to think and concentrate (called impaired cognition). This tends to be worse with larger radiation fields, tends to worsen over time, and is more of a problem in people who survive for several years after radiation therapy. It is difficult to know for certain whether impaired cognition results from the radiation or whether it might be due to the disease itself. Nevertheless, the possibility of impaired cognition is one of the main reasons why radiation therapy is often delayed until it is absolutely necessary.
Chemotherapy — Regardless of the initial form of therapy, low-grade gliomas generally progress over time; the time frame may be long, sometimes as long as ten years or more after the original diagnosis. The tumor may also develop an aggressive (more malignant) phase after a variable period of time. This aggressive phase is characterized by more rapid tumor growth and progressive worsening of tumor-related symptoms.
Treatment options are limited in the late phases of the disease since surgery and radiation therapy are unlikely to be useful or possible. In such cases, chemotherapy may be considered.
Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult’s normal cells are not actively growing, they are not affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair roots (follicles), and the lining of the gastrointestinal tract.
Effects of chemotherapy on these and other normal tissues cause side effects during treatment. In general, side effects are more frequent when two or more drugs are administered simultaneously (termed combination chemotherapy, see below) and with higher as compared to lower doses of chemotherapy. Most chemotherapy drugs that are used for the treatment of brain tumors are given into a vein, although some (temozolomide, for example) are effective when given by mouth.
Chemotherapy is not curative, but it can improve symptoms (for months rather than years) in some patients. Tumor shrinkage (which may be accompanied by an improvement in symptoms) has been seen in selected patients using various drugs or combinations, such as temozolomide (Temodar) or the “PCV” combination (procarbazine, lomustine, and vincristine). Patients with the oligodendroglioma subtype (especially those with the chromosome1p deletion) are most likely to benefit from chemotherapy; response rates in other types of low-grade gliomas have generally been disappointing.
The use of chemotherapy in conjunction with radiation therapy earlier in the course of low-grade glioma has not been adequately studied. Thus, benefit from this approach has not been established, and it should only be used in the setting of a clinical research study. (See ‘Clinical trials’ below.)
CLINICAL TRIALS — Progress in treating gliomas requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:
www.cancer.gov/clinicaltrials/learning/
www.cancer.gov/clinicaltrials/
SUMMARY — Low-grade gliomas are cancers that develop in the brain and tend to be slow-growing. Although people with these tumors are only rarely cured, most are able to maintain to work, attend school, and perform other tasks for a number of years. Careful management of seizures, brain swelling, and other complications with medications, combined with the timely use of surgery, radiation therapy, and perhaps chemotherapy, can help preserve a high quality of life and minimize disability.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient Level Information:
Patient information: High-grade glioma in adults
Professional Level Information:
Clinical manifestations and initial surgical approach to patients with malignant gliomas
Clinical presentation and diagnosis of brain tumors
Diagnosis and classification of low-grade gliomas
Management of low-grade glioma
The following organizations also provide reliable health information.
National Cancer Institute
1-800-4-CANCER
(www.cancer.gov/cancertopics/pdq/treatment/adultbrain/Patient, available in Spanish)American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)National Comprehensive Cancer Network
(www.nccn.com)American Cancer Society
1-800-ACS-2345
(www.cancer.org)American Brain Tumor Association
(www.abta.org)National Brain Tumor Foundation
(www.braintumor.org)Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.
About.com Cancer Forum
(file://cancer.about.com/forum)
REFERENCES
Claus EB, Black PM. Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973-2001. Cancer 2006; 106:1358.
DeAngelis LM. Brain tumors. N Engl J Med 2001; 344:114.
Piepmeier J, Baehring JM. Surgical resection for patients with benign primary brain tumors and low grade gliomas. J Neurooncol 2004; 69:55.
Bampoe J, Bernstein M. The role of surgery in low grade gliomas. J Neurooncol 1999; 42:259.
Shaw EG, Tatter SB, Lesser GJ, et al. Current controversies in the radiotherapeutic management of adult low-grade glioma. Semin Oncol 2004; 31:653.
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