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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. "Glioma" is the name of a tumor that develops from a glial cell.
In this article, we will discuss the symptoms, diagnosis, and treatment of low-grade gliomas, an important category of primary brain tumors. Information about high-grade gliomas can be found elsewhere (see "Patient education: High-grade glioma in adults (Beyond the Basics)"). More detailed information about low-grade gliomas is available by subscription. (See "Treatment and prognosis of IDH-mutant astrocytomas in adults".)
CLASSIFICATION OF PRIMARY BRAIN TUMORS — Brain tumor classification has changed as researchers have discovered more about tumor genetics. Likewise, the definition of low-grade glioma has become more complicated.
Before the year 2000, gliomas were classified based on their appearance under the microscope (histology). The two most common types of gliomas were astrocytoma and oligodendroglioma. Gliomas were further graded from 1 to 4 based on how aggressive they appeared under the microscope. Grades 1 and 2 were considered "low grade."
Since 2016, brain tumors have been classified and renamed based not only on their histologic appearance, but also on their genetic makeup. Two important genetic changes that determine how a glioma is classified are whether it has a "1p/19 deletion" and whether or not it has an isocitrate dehydrogenase (IDH) mutation. Both of these changes, if present, indicate a more favorable prognosis. In other words, people with a glioma that has a 1p/19q deletion or an IDH mutation tend to live longer than people with a glioma that looks the same under the microscope but does not have these changes. Other genetic changes have the opposite effect, meaning that some tumors that used to be called low-grade gliomas are now recognized to behave more like high-grade, or malignant, gliomas.
Therefore, in this topic, we use the term "low-grade glioma" to include grade 2 astrocytomas and oligodendrogliomas that have a favorable genetic makeup, based on the presence of a 1p/19q deletion, an IDH mutation, or both. Tumors with both of these changes are called "oligodendroglioma," even if they don't look exactly like an oligodendroglioma under the microscope. Low-grade glioma also includes some grade 1 tumors. The most common grade 1 glioma is called a pilocytic astrocytoma.
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 clinician 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, but an MRI usually gives a more detailed view of a tumor.
A head CT is sometimes 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 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.)
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 clinician 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 (brand name: 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 minimizes 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 "Treatment and prognosis of IDH-mutant astrocytomas in adults".)
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 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 clinicians 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 clinicians 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 clinician 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 clinician 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 clinician 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 sometimes delayed (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 — 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.
Chemotherapy is given along with radiation for certain types of low-grade gliomas. In other cases, it is used later in the course of illness, when there is evidence that the tumor has recurred and is causing symptoms.
Chemotherapy is not curative, but it can improve survival by several 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 (brand name: Temodar) or the "PCV" combination (procarbazine, lomustine, and vincristine). Patients with oligodendrogliomas are most likely to benefit from chemotherapy.
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 with lower doses of chemotherapy. Some chemotherapy drugs that are used for the treatment of brain tumors are given into a vein, and some (temozolomide, for example) are effective when given by mouth.
Recurrent disease — Regardless of the initial form of therapy, low-grade gliomas generally progress over time; the time frame may be long, sometimes as long as 10 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.
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:
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology.
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 chemotherapy, can help preserve a high quality of life and minimize disability.
WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Clinical presentation, diagnosis, and initial surgical management of high-grade gliomas
Overview of the clinical features and diagnosis of brain tumors in adults
Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors
Treatment and prognosis of IDH-mutant astrocytomas in adults
The following organizations also provide reliable health information.
●National Cancer Institute
●The American Society of Clinical Oncology
●American Cancer Society
●National Library of Medicine
●American Brain Tumor Association
●National Brain Tumor Foundation
●National Institute of Neurological Disorders and Stroke
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