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Patient education: High-grade glioma in adults (Beyond the Basics)

Patient education: High-grade glioma in adults (Beyond the Basics)
Author:
Tracy Batchelor, MD, MPH
Section Editor:
Patrick Y Wen, MD
Deputy Editor:
April F Eichler, MD, MPH
Literature review current through: Nov 2022. | This topic last updated: Aug 10, 2020.

HIGH-GRADE GLIOMA OVERVIEW — Primary brain tumors originate in the brain. These tumors are very different from secondary (or metastatic) brain tumors, which originally developed elsewhere in the body and spread (metastasized) to the brain.

Primary brain tumors mainly 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.

This article will discuss the symptoms, diagnosis, and treatment of high-grade (ie, malignant) gliomas, the largest subset of brain gliomas. Primary low-grade gliomas are discussed separately. (See "Patient education: Low-grade glioma in adults (Beyond the Basics)".)

CLASSIFICATION OF PRIMARY BRAIN TUMORS — Primary brain tumors are tumors that are classified by a pathologist according to their appearance under the microscope and by certain molecular and genetic markers. Gliomas are classified into four grades (I, II, III, and IV), and the treatment and prognosis depend upon the tumor grade.

Grade I or II tumors are termed low-grade gliomas. The term malignant or high-grade glioma refers to tumors that are classified as:

Grade III (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma)

Grade IV (glioblastoma)

Astrocytomas, oligodendrogliomas, and glioblastomas are further classified based on whether they have a genetic change in the isocitrate dehydrogenase (IDH) gene. If there is a mutation, the tumor is designated as IDH mutant, and if there is no mutation, the tumor is designated as IDH wildtype. IDH-wildtype tumors are more aggressive and behave like high-grade glioma.

HIGH-GRADE GLIOMA SYMPTOMS — Gliomas cause symptoms by invading (growing) into and/or creating pressure in nearby normal brain tissue. The most common symptoms include:

Cognitive symptoms like memory loss, personality change, confusion, speech problems.

Headache.

Seizures – Seizures occur in more than one-half of patients with grade III or grade IV gliomas. Seizures are caused by disorganized electrical activity in the brain. Medications are usually necessary to control seizures. A neurologist can be helpful in managing seizures related to high-grade gliomas.

Other common symptoms of brain tumors include weakness, balance problems, visual symptoms, and changes in sensation.

HIGH-GRADE GLIOMA TESTS

Imaging studies — If your healthcare provider is concerned about your symptoms, s/he may recommend a scan of the brain. This can be done using magnetic resonance imaging (MRI) or computed tomography (CT). Both tests provide a very detailed image of the brain. Usually, a contrast dye is also given through a vein for the CT or MRI to better visualize the brain. MRI generally provides a more detailed scan of the tumor. However, a CT or MRI cannot determine for sure if a mass is a brain tumor.

Surgery — The only way to determine the type of tumor with certainty is for a neurosurgeon to remove a piece of the tumor during surgery (resection). A pathologist will then examine the tumor tissue under a microscope.

Biopsy — A biopsy may be done without a larger surgery; this approach is preferred if the tumor is located within a critical area of the brain or if you are too sick for surgery. In these circumstances, a procedure called a stereotactic needle biopsy is used to take a sample of the tumor by inserting a needle through the skull into the brain itself.

HIGH-GRADE GLIOMA INITIAL TREATMENT — Treatment of a high-grade glioma includes measures to relieve symptoms and eliminate or control the tumor. This may include surgery, radiation, and/or chemotherapy. (See "Initial treatment and prognosis of IDH-wildtype glioblastoma in adults" and "Radiation therapy for high-grade gliomas" and "Clinical presentation, diagnosis, and initial surgical management of high-grade gliomas".)

Because there are not curative treatments for most types of high-grade glioma, many people are encouraged to participate in a clinical trial, if possible. (See 'Clinical trials' below.)

Symptom management — Seizures and swelling in the brain (cerebral edema) can cause serious neurologic symptoms that are occasionally life threatening. Although treatment of the tumor may eventually alleviate these symptoms, treatments aimed at controlling the symptoms are effective and may be required:

Seizures – Antiseizure medications can usually control seizures caused by a brain tumor.

Cerebral edema – Cerebral edema is swelling in the brain that may cause neurologic symptoms. Symptomatic edema is treated with glucocorticoids (also called steroids), most commonly dexamethasone (Brand name: Decadron).

To minimize side effects, the dose of dexamethasone is decreased gradually to the lowest level that controls symptoms. Long-term dexamethasone may require use of a preventive antibiotic to protect against a certain type of lung infection.

Hydrocephalus – Cerebrospinal fluid normally surrounds and cushions the brain. Hydrocephalus occurs when the flow of cerebrospinal fluid is blocked, which increases pressure within the brain. This is uncommon, but treatment may be required in the form of surgery to place a tube in the brain cavities (called a shunt) to bypass the blockage and lower the pressure within the brain.

Deep venous thrombosis – People with high-grade glioma can develop blood clots in the leg, called deep venous thrombosis, or "DVT." DVT can cause swelling, pain, and warmth in the calf. Blood clots can also travel to the lungs and cause pulmonary embolism, or "PE." DVT and PE are usually treated with anticoagulant medicines.

Surgery — The initial treatment of high-grade glioma usually involves removing as much of the tumor as safely possible with surgery. The amount of tumor that can be removed is determined by the tumor's size and location, and by how much normal brain will be potentially injured as a result of surgery. The standard approach is to remove as much of the tumor as possible, while sparing areas of the normal brain that control critical functions such as speech or balance.

The neurosurgeon may be guided by MRI in the operating room ("intraoperative MRI") or by a special dye that helps to view the tumor under a microscope during surgery. Sometimes the neurosurgeon may recommend a "functional" brain MRI before the operation to better understand where different neurologic functions (speech, movement) are controlled in your brain. These areas can then be avoided at the time of the surgery to remove the tumor.

Surgery may not be possible if the tumor is located in a part of the brain that controls critical functions or if you are in poor health. In these circumstances, radiation may be recommended as an alternative to surgery. (See 'Radiation' below.)

Radiation — Even when the entire tumor appears to have been removed, almost all high-grade gliomas eventually come back. This is because tumor cells have grown into the surrounding normal brain and cannot be seen with standard MRI scans. Radiation therapy uses high-energy x-rays to kill cancer cells and is usually recommended following surgery to kill any remaining tumor cells. This treatment is called adjuvant radiation. Radiation can help to delay a recurrence of the tumor, allowing you to live longer.

Radiation is generally given as a series of once-daily treatments (called fractions) over several weeks. This approach helps to kill the greatest number of tumor cells and minimize side effects on normal brain cells. The area where the radiation is delivered (called the radiation field) is carefully calculated to include the smallest possible amount of normal brain in the radiation field as possible.

Most brain tumors that grow back are within 2 cm (1 inch) of the original tumor location. As a result, radiation is usually delivered to the "involved field" (the original area of the tumor plus a small margin) rather than the whole brain.

Side effects — Radiation may kill normal brain cells as well as tumor cells, although tumor cells are somewhat more sensitive to the radiation. Damage to normal brain cells might be subtle, affecting mental sharpness and the ability to think and perform complex tasks (called cognitive impairment). Cognitive impairment tends to be more severe with larger radiation fields, tends to worsen over time, and is more of a problem in people who survive for several years after radiation treatments to the brain.

It is not always possible to know if cognitive impairment is caused by radiation or a recurrence of the high-grade glioma. Some experts advise detailed testing of thinking and memory, called neuropsychological testing, early in the treatment course. That way they can understand how things have changed with repeat testing in the future.

Radiation may also negatively affect control of body hormones, which may produce symptoms. An endocrinologist or neuroendocrinologist may be consulted to help manage hormone function.

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. 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 blood cells are produced), the hair, and the lining of the gastrointestinal tract. Effects of chemotherapy on these and other normal tissues cause side effects during treatment.

When used in combination with radiation therapy and surgery, chemotherapy may improve survival and quality of life in some patients with high-grade gliomas. The drug that is most widely used for high-grade glioma is temozolomide (Brand name: Temodar).

Temozolomide is usually taken by mouth daily with radiation and then for up to six monthly cycles (five consecutive days every four weeks) after the radiation.

Electric fields — A battery-powered device that provides low-strength electric fields around the tumor (Optune) is another treatment option. The device is applied directly to the scalp after the head is shaved and it is supposed to be worn for at least 18 hours per day. In a clinical trial, people with grade IV gliomas who wore the device during monthly cycles of temozolomide had better survival compared with people who did not wear the device.

TREATMENT AFTER RECURRENCE — High-grade gliomas "recur" (ie, regrow) in most patients. There is less consensus about the potential benefits of treatment when the tumor recurs. If you decide to undergo treatment, you must consider the risks of treatment as well as the potential impact on your quality of life.

Treatment of a high-grade glioma that has recurred does not always improve survival compared with supportive care alone (ie, treatments to ease pain and other symptoms). (See 'Palliative care and end-of-life care' below.)

You may benefit from retreatment if you have:

Good overall health

A smaller amount of tumor present

A longer interval (eg, one year versus less than one year) between your original treatment and the recurrence

Options available for retreatment include surgery, various forms of radiation, chemotherapy, and electric fields.

Surgery — It is not clear which people with recurrent high grade-glioma will benefit from surgery. The most important factor that predicts a longer survival after reoperation is your overall health. Other factors that increase the chances of prolonged survival include a younger age, a long interval between operations (eg, one year or more), and removing a larger amount of tissue with the second surgery. Sometimes surgery with implantation of a biodegradable wafer that releases local chemotherapy can be used.

Radiation — Although there are exceptions, giving additional radiation is not usually possible in people with high-grade glioma recurrence because of the high risk of damage to normal brain tissue. Special techniques, such as stereotactic radiosurgery or brachytherapy, may permit additional radiation to be directed selectively to the tumor. However, there is no proof that these radiation treatments improve survival or provide any benefit to the patient compared with supportive care alone.

Chemotherapy — Chemotherapy is not as effective for recurrent high-grade gliomas as it is for treatment when newly diagnosed. Oral lomustine (Brand name: Gleostine) is an option in this situation. Another course of temozolomide is also an option for some people. Enrollment in a clinical trial is often recommended, when possible.

Bevacizumab — Bevacizumab (Brand name: Avastin) is an antibody (a type of protein) that targets a protein called vascular endothelial growth factor (VEGF). VEGF causes a growing cancer to develop its own blood supply, which is essential for the tumor to grow and spread. Bevacizumab disrupts the process of new blood vessel formation, thereby depriving the tumor of its supply of nutrients.

Bevacizumab may be used alone or in combination with chemotherapy. However, bevacizumab can cause some serious side effects, including high blood pressure, bleeding, stroke, and infection.

Electric fields — A battery-powered device that provides low-strength electric fields around the tumor (Optune) is another treatment option. However, in a clinical trial, people with recurrent grade IV gliomas who wore the device had similar survival compared with people who took only chemotherapy.

OLIGODENDROGLIOMAS — Oligodendrogliomas represent an important subset of grade III gliomas and account for approximately 10 percent of all primary gliomas. These tumors have lost parts of chromosomes and have a very high likelihood of responding to treatment, especially a combination of chemotherapy agents (PCV: procarbazine, CCNU, vincristine), allowing the person a longer survival.

PALLIATIVE CARE AND END-OF-LIFE CARE — In most people with high-grade glioma, the disease cannot be cured. Involvement of a palliative care physician early in the treatment course can be helpful and has proven beneficial in other types of cancer. Deciding when to stop treating the cancer can be difficult and should involve the patient, family, friends, and the healthcare team.

Ending cancer treatment does not mean ending care for the patient. Hospice care is frequently recommended when a person is unlikely to live longer than six months. Hospice care involves treatment of all aspects of a patient and family's needs, including the physical (eg, pain relief), psychological, social, and spiritual aspects of care. This care may be given at home or in a nursing home or hospice facility and usually involves multiple care providers, including a physician, a registered nurse, a nursing aide, a chaplain or religious leader, a social worker, and volunteers.

These providers work together to meet the patient and family's needs and significantly reduce their suffering. (See "Hospice: Philosophy of care and appropriate utilization in the United States".)

CLINICAL TRIALS — Progress in treating high-grade 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/about-cancer/treatment/clinical-trials

https://clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (https://www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).

WHERE TO GET MORE INFORMATION — Your healthcare 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 healthcare 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.

Patient education: Brain cancer (The Basics)
Patient education: Astrocytoma (The Basics)
Patient education: Glioblastoma (The Basics)

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.

Patient education: Low-grade glioma in adults (Beyond the Basics)

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.

Treatment and prevention of venous thromboembolism in patients with brain tumors
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
Diffuse intrinsic pontine glioma
Intracranial ependymoma and other ependymal tumors
Focal brainstem glioma
Treatment and prognosis of IDH-mutant astrocytomas in adults
Seizures in patients with primary and metastatic brain tumors
Optic pathway glioma
Molecular pathogenesis of diffuse gliomas
Initial treatment and prognosis of IDH-wildtype glioblastoma in adults
Radiation therapy for high-grade gliomas
Hospice: Philosophy of care and appropriate utilization in the United States

The following organizations also provide reliable health information.

National Cancer Institute

     1-800-4-CANCER
     (www.cancer.gov/types/brain/patient/adult-brain-treatment-pdq, available in Spanish)

American Society of Clinical Oncology

     (www.cancer.net/)

American Cancer Society

      1-800-ACS-2345

     (www.cancer.org)

American Brain Tumor Association

     (www.abta.org)

National Brain Tumor Society

     (https://braintumor.org/)

This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2023 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.
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