Patient information: High-grade glioma in adults (Beyond the Basics)
- Tracy Batchelor, MD, MPH
Tracy Batchelor, MD, MPH
- Giovanni Armenise Professor of Neurology
- Harvard Medical School
HIGH-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.
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 information: Primary 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. 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 oligoastrocytoma, anaplastic ependymoma)
●Grade IV (glioblastoma)
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
●Seizures – Seizures occur in more than one-half of patients with grade III gliomas and about one-fourth of patients with grade IV gliomas. Seizures are caused by disorganized electrical activity in the brain. Medications are usually necessary to control seizures.
Other common symptoms of brain tumors include muscle weakness, 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 MRI or 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. However, a CT or MRI cannot determine for sure if a mass is a cancerous tumor.
Biopsy — The only way to determine the type of tumor with certainty is for a neurosurgeon to remove a piece of the tumor (resection), usually during surgery. A pathologist will then examine the biopsy under a microscope.
However, a biopsy may be done without 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 postoperative therapy for glioblastoma and anaplastic astrocytoma" and "Adjuvant radiation therapy for high-grade gliomas" and "Clinical manifestations and initial surgical approach to patients with 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 symptoms that may be life-threatening. Although treatment of the tumor may eventually alleviate these symptoms, treatments aimed at controlling the symptoms may be required:
●Seizures – Anti-seizure medications can usually control seizures caused by a brain tumor.
●Cerebral edema – Cerebral edema is swelling in the brain that may cause neurologic symptoms. It 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.
●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. Treatment may require surgery to place a tube in the skull (called a shunt) to bypass the blockage and lower the pressure within the brain.
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 damaged 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.
Unfortunately, high-grade gliomas always have microscopic tumor cells that grow beyond the edge of the tumor. As a result, the tumor eventually regrows and few people with high-grade gliomas are cured with surgery alone. Radiation is typically recommended after surgery to kill any remaining tumor cells.
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. Radiation therapy uses high energy x-rays to kill cancer cells and is usually recommended following surgery to kill 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 (one 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 is often 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. Radiation may also affect control of body hormones, which may produce symptoms.
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 are most widely used for high-grade glioma include temozolomide (Brand name: Temodar®).
Temozolomide is usually taken by mouth daily with radiation and then for five consecutive days every four weeks after the radiation.
TREATMENT AFTER RECURRENCE
High-grade gliomas recur or regrow in most patients. There is controversy 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 to supportive care alone (ie, treatments to ease pain and other symptoms) (see '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, and chemotherapy.
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.
The average survival of people who undergo surgery for recurrent grade IV gliomas ranges from 14 to 36 weeks. It is somewhat longer for patients with grade III tumors (56 to 88 weeks). Placing a biodegradable chemotherapy wafer (Gliadel®) during surgery may prolong survival further. In one study, people who had a Gliadel® wafer placed had a significantly longer median survival (31 versus 23 weeks) compared to people who had a placebo wafer . However, there are potential side effects from the wafer including brain swelling and infection.
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 directly selectively to the tumor. However, there is no proof that these radiation treatments improve survival or provide any benefit to the patient compared to supportive care alone.
Chemotherapy — Chemotherapy is not as effective for recurrent high-grade gliomas as it is for treatment when newly diagnosed. Oral CCNU (lomustine) is an option in this situation. 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.
Oligodendrogliomas represent an important subset of grade III gliomas and account for about 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.
END OF LIFE CARE
In many people with high-grade glioma, the disease cannot be cured. 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 suffering. This care may be given at home or in a nursing home or hospice facility and usually involves multiple care providers, including a physician, registered nurse, 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. For more information about hospice, see www.hospicenet.org. (See "Hospice: Philosophy of care and appropriate utilization in the United States".)
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:
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/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.
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.
Anticoagulant and antiplatelet therapy in patients with brain tumors
Classification of gliomas
Clinical manifestations and initial surgical approach to patients with high-grade gliomas
Clinical presentation and diagnosis of brain tumors
Diagnosis and classification of low-grade gliomas
Diffuse pontine glioma
Experimental treatment approaches for high-grade gliomas
Focal brainstem glioma
Management of low-grade glioma
Seizures in patients with primary and metastatic brain tumors
Optic pathway glioma
Pathology and molecular pathogenesis of diffuse gliomas
Initial postoperative therapy for glioblastoma and anaplastic astrocytoma
Adjuvant 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
(www.cancer.gov/cancertopics/pdq/treatment/adultbrain/Patient, available in Spanish)
●American Society of Clinical Oncology
●National Comprehensive Cancer Network
●American Cancer Society
●American Brain Tumor Association
●National Brain Tumor Foundation
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
- Pathology and genetics of tumours of the nervous system. In: World Health Organization Classification of Tumours of the Nervous System, Editorial and Consensus Conference Working Group, Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds), IARC Press, Lyon, France 2007.
- Hau P, Baumgart U, Pfeifer K, et al. Salvage therapy in patients with glioblastoma: is there any benefit? Cancer 2003; 98:2678.
- Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 1995; 345:1008.
- Statistical Report: Primary Brain Tumors in the United States, 1997-2001. Central Brain Tumor Registry of the United States; 2004.
- Chang SM, Parney IF, Huang W, et al. Patterns of care for adults with newly diagnosed malignant glioma. JAMA 2005; 293:557.
- Walker MD, Green SB, Byar DP, et al. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 1980; 303:1323.
- Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 2002; 359:1011.
- Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol 2003; 5:79.
- Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.