Primary Brain Tumors
Primary brain tumors are tumors that start in the brain. There are many types and subtypes of primary brain tumors; some are benign, others malignant. Examples include gliomas, meningomas, medullablastomas, pituitary adenomas, and central nervous system lymphomas.
The exact causes of primary brain tumors are unknown. Genetic factors and inherited disorders play a role in some types of brain tumors.
Risk factors for brain tumors vary according to the type of tumor. Some types of tumors are more prevalent in men than in women. Some types of brain tumors usually occur in children, while others are more common in older people.
Survival rates in people with brain tumors depend on many different variables:
Brain tumors produce a variety of symptoms including headache, seizure, and neurological changes. Symptoms may be subtle and gradually become worse or they may occur very rapidly.
Diagnosis of brain tumor involves a neurological exam and various types of imaging tests. Imaging techniques include magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scan. Biopsies may be performed as part of surgery to remove a tumor, or as a separate diagnostic procedure.
The standard approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation treatment, or chemotherapy. Such treatments are typically used in combination with each other.
Brain tumors are composed of cells that exhibit abnormal growth in the brain.
They can be benign (noncancerous, meaning that they do not spread elsewhere or invade surrounding tissue) or malignant (cancerous).
Cancerous (malignant) brain tumors are classified as either primary or secondary tumors. Primary tumors start in the brain. Secondary tumors spread to the brain from another site such as the breast or lung. This report focuses on primary malignant brain tumors.
Primary brain tumors can be either benign (non-cancerous) or malignant (cancerous).
Benign Brain Tumors. Benign tumors represent half of all primary brain tumors. Their cells look relatively normal, grow slowly, and do not spread (metastasize) to other sites in the body or invade brain tissue. Benign tumors can still be serious if they are in vital areas in the brain. They can be life-threatening if they exert pressure on sensitive nerve tissue or if they increase pressure within the brain. Fortunately, most benign brain tumors can be successfully treated.
Malignant Brain Tumors. A primary malignant brain tumor is cancer that originates in the brain itself. Although primary brain tumors often transmit cancerous cells to other sites in the central nervous system (the brain or spine), they rarely spread to other parts of the body.
Brain tumors are generally named and classified according to either of the following:
The biologic diversity of these tumors, however, makes classification difficult.
A secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Solitary metastasized brain cancers may occur but are less common than multiple tumors. Most often, cancers that spread to the brain to cause secondary brain tumors originate in the lung, breast, kidney, or from melanomas in the skin.
All secondary (metastatic) brain tumors are malignant. This report discusses primary malignant brain tumors.
About 80% of malignant primary brain tumors are known collectively as gliomas. Gliomas are not a specific type of cancer but are a term used to describe tumors that originate in glial cells. Glial cells are the building-block cells of the connective, or supportive, tissue in the central nervous system.
Gliomas are classified into four grades that reflect the degree of malignancy. Grades I and II are considered low-grade and grades III and IV are considered high-grade:
Astrocytomas are primary brain tumors derived from astrocytes, which are star-shaped glial cells. Astrocytomas account for about 60% of all malignant primary brain tumors. Astrocytoma tumor types by grade include:
Oligodendrogliomas develop from oligodendrocyte glial cells, which form the protective coatings around nerve cells. Oligodendrogliomas are classified as either low-grade (grade II) or anaplastic (grade III). Pure oligodendrogliomas are rare. In most cases they occur in mixed gliomas. Oligodendrogliomas usually occur in younger and middle-aged adults.
Ependymomas are derived from ependymal cells, which line the ventricles (fluid-filled cavities) in the lower part of the brain and the central canal of the spinal cord. They are one of the most common types of brain tumor in children. They can also occur in adults in their 40s and 50s. Ependymomas are divided into four categories: Myxopapillar ependymomas (grade I), subependymomas (grade I), ependymomas (grade II), and anaplastic aependymomas (grades III and IV).
Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.
Gliomas may also contain cancer cells derived from brain cells other than glial cells.
Location of Gliomas. Gliomas are also described by the location of the tumor. Examples include:
Malignant types of non-glioma brain tumors include:
Benign types of non-glioma brain tumors include:
Only 5 - 10% of primary brain tumors are associated with genetic disorders. These inherited conditions and associated genes include:
Certain types of brain tumors are specifically linked with these genetic conditions. For example, neurofibromatosis 1 is associated with about 15% of cases of pilocytic astrocytomas, the most common type of childhood glioma.
Most genetic abnormalities that cause brain tumors are not inherited but occur as a result of environmental or other factors that affect genetic materials (DNA) in the cells. Researchers are studying various environmental factors (such as viruses, hormones, chemicals, and radiation) that may trigger the genetic disruptions that lead to brain tumors in susceptible individuals. They are also working to identify the specific genes that are affected by these environmental triggers.
Primary malignant brain tumors account for about 2% of all cancers. However, brain and spinal cord tumors are the second most common type of cancer in children (after leukemia). According to the American Cancer Society, about 23,000 people in the United States are diagnosed each year with a malignant brain or spinal cord tumor.
In general, brain tumors are slightly more likely to occur in men than in women. Some specific types of brain tumors, such as meningiomas, are more common in women.
Most brain tumors in adults occur between the ages of 65 - 79. Brain tumors also tend to occur in children younger than age 8. In children, malignant brain tumors are the leading cause of death from solid tumors (non-blood cell cancers).
The risk for primary brain tumors in Caucasians is higher, as much as double the risk for gliomas, than in people of other races.
Exposure to ionizing radiation, usually from radiation therapy, is the only environmental risk factor that has been definitively linked to brain tumors. People who receive radiation therapy to the head during cancer treatment have an increased risk of developing brain tumors 10 - 15 years later. Workers in the nuclear industry are also at increased risk.
Despite much research, there is no evidence that electromagnetic field exposure from power lines or household appliances poses any risk. Several recent epidemiological studies have examined the cancer risk of wireless devices such as cellular (mobile) phones, which emit radiofrequency (RF) energy. To date, the studies do not show an association between cell phone use and common brain tumors like gliomas and meningiomas. However, more research is needed to examine potential long-term effects, particularly for children and adolescents.
Researchers have also investigated a number of metals and chemicals including vinyl chloride, petroleum products, lead, arsenic, mercury, and pesticides. To date, there has been no clear evidence that implicates any specific industrial chemical or metal. Research continues.
People with impaired immune systems have an increased risk of developing central nervous system lymphomas. Organ transplantation, HIV infection, and chemotherapy are some medical factors that can weaken the immune system.
Recent advances in surgical and radiation treatments have significantly extended average survival times of patients with brain tumors. These new treatments can often help reduce the size and progression of malignant gliomas.
The survival rates in people with brain tumors depend on many different variables:
Patients with some types of tumors have relatively good survival rates. Five-year survival rates for patients with ependymoma and oligodendroglioma are, respectively, 91% and 85% for people ages 20 - 44, and 84% and 64% for patients ages 55 - 64. For children, the survival rate for these brain tumors are about 75% and 95%.
Glioblastoma multiforme has the worst prognosis with 5-year survival rates of only 14% for people ages 20 - 44, and 1% for patients age 55 - 64. The 5-year survival rate for children is about 20%. Survival rates tend to be highest for younger patients and decrease with age.
Malignant primary brain tumors are classified according to tumor grade. Grade I is the least cancerous, and Grades III and IV are the most dangerous. Grading a tumor can help predict its growth rate and tendency to spread. Grading is based on the appearance of the tumor cells as seen under a microscope.
In tumors that contain a mixture of different-grade cells, the tumor is graded according to the highest-grade cells in the mixture, even if there are very few of them.
Brain tumors can cause seizures, mental changes, and mood, personality, and emotional changes. Tumors may also impair muscle function, hearing, vision, speech, and other neurologic activities. Such effects can be very difficult for both patients and caregivers. Numerous treatments are available that can help alleviate these complications. Patients and family members should discuss these options with their doctors.
Effects in Children. Advancements in treatment have dramatically increased survival rates for children with brain tumors. About 75% of children survive at least 5 years after being diagnosed with a brain tumor. Unfortunately, many childhood brain tumor survivors are at risk for long-term neurological complications.
Children younger than age 7 (and particularly those younger than age 3 years) appear to have the greatest risk for cognitive problems. These problems may result from the tumor and from treatment (cranial radiation therapy, chemotherapy that penetrates the blood-brain barrier). Long-term cognitive problems include difficulties with attention and concentration, memory, mental processing of information, visual perception skills, and problems with planning, insight, initiative, and organizational competencies. Parents need to make sure that children receive appropriate supportive services and educational accommodation at their schools.
Brain tumors can produce a variety of symptoms, ranging from headache to seizure. They are great mimics of other neurologic disorders. Symptoms occur if the tumor directly damages the nerves in the brain or central nervous system, or if its growth puts pressure on the brain. Symptoms may be subtle and gradually become worse, or they may occur very rapidly.
Headache is probably the most frequent symptom of a brain tumor. However, headaches (especially tension-type and migraine) are very common, and the great majority of headaches are not caused by brain tumors. Most headaches associated with brain tumors are accompanied by other neurological symptoms.
Headaches caused by brain tumors vary depending on the tumor's location and other factors. Symptoms that may be associated with brain tumors include:
Gastrointestinal symptoms, including nausea and vomiting, are also common.
About half of patients with brain tumors have a seizure. It is a common symptom of brain tumors in older adults. (However, very few first seizures are caused by a brain tumor.)
Sometimes the only symptoms of brain tumors are mental changes, which may include:
A neurological exam is usually the first test given when a patient complains of symptoms that suggest a brain tumor. The exam includes checking eye movements, hearing, sensation, muscle strength, sense of smell, and balance and coordination. The doctor will also test mental state and memory.
Advanced imaging techniques are an essential part of the diagnosis of brain tumors.
Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is the standard imaging procedure for diagnosing a brain tumor. It provides pictures from various angles that can help doctors to construct a three-dimensional image of the tumor. It gives a clear picture of tumors near bones, smaller tumors, brain stem tumors, and low-grade tumors. MRI is also useful during surgery to show tumor bulk, for accurately mapping the brain, and for detecting response to therapy.
Computed Tomography. Computed tomography (CT) uses a sophisticated x-ray machine and a computer to create a detailed picture of the body's tissues and structures. It is not as sensitive as an MRI in detecting small tumors, brain stem tumors, and low-grade tumors. It is useful in certain situations, however. Often, doctors will inject the patient with a contrast material to make it easier to see abnormal tissues. A CT scan helps locate the tumor and can sometimes help determine its type. It can also help detect swelling, bleeding, and associated conditions. In addition, computed tomography is used to evaluate the effectiveness of treatments and watch for tumor recurrence.
Positron Emission Tomography. Positron emission tomography (PET) provides a picture of the brain's activity rather than its structure by tracking a sugar that has been labeled with a radioactive tracer. It is sometimes able to distinguish between recurrent tumor cells and dead cells or scar tissue caused by radiation therapy. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. Data from PET may also help improve the accuracy of newer radiosurgery techniques. PET scans are often done along with a CT scan.
Other Imaging Techniques. Numerous other advanced or investigational imaging techniques include:
A spinal tap (lumbar puncture) is used to obtain a sample of cerebrospinal fluid, which is examined for the presence of tumor cells. Spinal fluid may also be examined for the presence of certain tumor markers (substances that indicate the presence of a tumor). However, most primary brain tumors do not have identified tumor markers.
An imaging scan should generally be performed before a lumbar procedure to make sure that the procedure can be performed safely.
A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor and examined under a microscope for malignancy. The results of the biopsy also provide information on the cancer cell type. Biopsies may be performed as part of surgery to remove a tumor, or as a separate diagnostic procedure.
In some cases, such as with brain stem gliomas, a standard biopsy might be too hazardous because removing any healthy tissue from this area can affect vital functions. In these cases, surgeons can use alternative techniques such as needle biopsy and stereotaxic biopsy. Stereotaxic biopsy is a computer-directed type of needle biopsy that uses images provided from MRI or CT scans to provide precise information on the tumor's location.
The standard approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation therapy (also called radiotherapy), or chemotherapy. Such treatments are used alone or, more commonly, in combination with one another.
The intensity, combination, and sequence of treatments depend on the brain tumor type (there are over 100 types of brain tumors), its size and location, and patient age, health status, and medical history. Unlike other types of cancer, there is no formal staging system for brain tumors.
With some very slow-growing cancers, such as those that occur in the midbrain or optic nerve pathway, patients may be closely observed and not treated until the tumor shows signs of growth.
TTF Therapy. Tumor Treating Fields (TTF) therapy uses a low-intensity electrical field to disrupt the rapid division of cancer cells. In 2011, the FDA approved the NovoTTF-100A System to treat adults with glioblastoma multiforme that has recurred or progressed despite chemotherapy and radiation. This device uses electrodes placed on the patient’s scalp to deliver alternating electrical fields to the tumor site. The device is portable and can be used at home
Investigational Treatments. Patients can enroll in clinical trials that are researching new treatments for brain tumors.
Surgery is usually the first step in treating most brain tumors. (In some cases, such as most brain stem gliomas and other tumors located deep inside the brain, it may be too dangerous to perform surgery.) The objective of most brain tumor surgeries is to remove or reduce as much of the tumor's bulk as possible. Reducing the tumor's size can help make other treatments, particularly radiotherapy, more effective.
The standard surgical procedure is called craniotomy.
In stereotactic craniotomy, imaging techniques, such as CT and MRI scans, are used along with surgery to help map the area of the tumor in the brain.
Relatively benign, grade I gliomas may be treated only by surgery. Most malignant tumors require additional treatments, including repeat surgery.
Sometimes a brain tumor can create blockage and cerebrospinal fluid accumulates excessively in the skull, causing increased intracranial pressure. In these cases, a surgeon may implant a ventriculoperitoneal shunt (VP) to help drain the fluid. The procedure involves placing a thin catheter into a brain ventricle and connecting it to a catheter that is tunneled into the abdominal (peritoneal) cavity. A pump that controls the flow of fluid is attached to both catheters.
The most serious concern of brain surgery is preserving brain function. Surgeons will try to be conservative in their approach so as to limit removing tissue that may cause a loss of function. Bleeding and blood clots are other complications. Postsurgical complications include swelling in the brain, which is typically treated with corticosteroid drugs. Steps are taken to reduce the risk of blood clots during the postoperative period.
Radiation therapy, also called radiotherapy, plays a central role in the treatment of most brain tumors.
Various radiation treatments are used. Radiation is usually given externally, from a source outside the body that directs radiation beams. In some cases, internal radiation may be used as a booster to external-beam radiation. Internal radiation (also called interstitial radiation) generally involves brachytherapy, which uses radioactive "seeds" implanted directly in the tumor site.
Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may need radiation, since they may become life threatening if their growth is not controlled.
Radiotherapy When Surgery Is Not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.
Radiotherapy and Chemotherapy (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial for some patients with high-grade tumors.
Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues on an outpatient basis about 5 days per week for 6 weeks. Older adults tend to have a more limited response to external-beam radiation therapy than younger people. Conventional external-beam radiation techniques include:
Stereotactic radiosurgery, also called stereotactic radiotherapy or stereotaxy, is an alternative to conventional radiotherapy that allows highly targeted radiation to be delivered directly to small tumors while avoiding healthy brain tissue. Stereotactic radiosurgery is radiation therapy, not surgery. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife.
Benefits of stereotactic radiosurgery include:
Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:
Once the preliminary planning stage has been completed, treatment begins. Several advanced machines, such as the gamma knife and adapted linear accelerator (LINAC), are used with stereotaxy to deliver very focused beams of radiation. Actual treatment takes about 15 minutes to 2 hours:
Researchers are studying drugs that may be used along with radiation to increase the effectiveness of the treatment.
Radioprotectors. Drugs such as amifosistine (Ethyol, generic) may protect healthy cells during radiation.
Radiosensitizers. Drugs such as fluorouracil (5-FU) and cisplatin (Platinol, generic) may help make cancerous cells more sensitive to radiation.
Common Side Effects. Side effects of radiotherapy vary depending on the tumor type and radiation treatment. Side effects can include hair loss, fatigue, headaches, and nausea and vomiting. Skin irritation and sensitivity may develop in the areas being treated. Brain swelling (edema) is another common radiotherapy side effect, which can sometimes cause an increase in neurologic symptoms. Edema can be treated with steroids.
Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in some patients treated with intensive radiation. Radiation necrosis can cause brain swelling and reduction in mental functions. The condition is treated with steroids. If steroids prove ineffective, surgery may be required to remove the damaged tissue.
New Tumors. Radiation therapy for childhood cancer is the most important risk factor for developing new brain and spinal column tumors. The risk appears greatest for children who received radiation therapy before age 5. The risk of second primary tumors increases in relation to the radiation dose used to treat the first cancer.
Stroke. Survivors of childhood brain tumors who were treated with high doses of cranial radiation (especially doses greater than 50Gy) may be at increased risk of having a stroke later in life.
Chemotherapy uses drugs to kill or alter cancer cells. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs have a hard time passing into the brain because of the blood-brain barrier that normally protects the brain from harmful chemicals. In addition, not all types of brain tumors respond to chemotherapy. In general, chemotherapy for brain tumors is usually administered following surgery or radiation therapy.
The type of drug determines how it is administered. "Systemic delivery" drugs, which pass to the brain from the bloodstream, may be given by mouth, injected into a vein through an IV, or injected into an artery or a muscle. "Local delivery" drugs are placed within or around the brain tumor.
Newer delivery methods to overcome some of these problems include:
Many different drugs, and drug combinations, are used for chemotherapy. Standard ones include:
Temozolomide (Temodar, generic). Temozolomide is used for adult patients with anaplastic astrocytoma that did not respond to other treatments. It is used during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. The current first-line treatment for patients with glioblastoma is combined radiotherapy and temozolomide, followed by monthly doses of temozolomide after radiation treatment ends. The drug may work best for patients with a specific genotype. Temozolomide's side effects are relatively minor, but may include constipation, nausea and vomiting, fatigue, and headache. The drug is taken by mouth as a pill.
Carmustine (BCNU, BiCNU). Carmustine is used to treat many types of brain tumors, including glioblastoma, medulloblastoma, and astrocytoma. Carmustine is usually administered into the vein by IV. It can also be delivered through a wafer implant (Gliadel), which is surgically placed into the brain cavity after tumor removal. If carmustine is administered intravenously, side effects may include nausea and vomiting, fatigue, respiratory problems, and lung scarring (pulmonary fibrosis). Intravenous carmustine may cause bone marrow impairment, which results in decreased production of blood cells (a condition called myelosuppression). If carmustine is delivered through a wafer, side effects may include seizures, brain swelling, and infection within the brain cavity.
PCV Drug Regimen. PCV is an abbreviation for a chemotherapy regimen that combines procarbazine (Matulane), lomustine (Ceenu, CCNU), and vincristine (Oncovin, generic). PCV is commonly used to treat oligodendrogliomas and mixed oligoastrocytomas. The drugs may also be used alone or in other combinations. Procarbazine and lomustine are taken by mouth. Vincristine is given by either injection or IV. These drugs can cause significant side effects, including a drop in blood cell counts, nausea and vomiting, constipation, fatigue, and mouth sores. Procarbazine can cause high blood pressure when taken with foods high in tyramine. Patients should avoid foods such as beer, red wine, cheese, chocolate, processed meat, yogurt, and certain fruits and vegetables.
Platinum-Based Drugs. Cisplatin (Platinol, generic) and carboplatin (Paraplatin, generic) are standard cancer drugs that are sometimes used to treat glioma, medulloblastoma, and other types of brain tumors. These drugs are delivered by IV. In addition to nausea and vomiting, carboplatin can cause hair loss, and cisplatin can cause muscle weakness.
Other Chemotherapy Drugs. Researchers are investigating whether drugs used to treat other types of cancer may have benefits for brain tumors. These drugs include:
Irinotecan (Camptostar, generic) is another cancer drug that is being studied in combination treatment.
Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells they can cause severe side effects. Targeted biologic therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, these biologic drugs may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotype.
Bevacizumab (Avastin). Bevacizumab (Avastin) is a biologic drug that blocks the growth of blood vessels that feed tumors (a process called angiogenesis). It is approved for the treatment of glioblastoma in patients whose brain cancer has continued to progress after prior treatment with chemotherapy and radiation. Bevacizumab was the first targeted therapy approved for brain tumors, and the first new treatment for glioblastoma in more than a decade. Some recent studies have questioned its effectiveness.
Investigational Targeted Therapies. Targeted therapies being tested in clinical trials include:
Some tumors, particularly medulloblastomas, interfere with the flow of cerebrospinal fluid and cause hydrocephalus (accumulation of fluid in the skull), which in turn causes a build-up fluid in the ventricles (the cavities) in the brain. Symptoms of peritumoral edema include nausea and vomiting, severe headaches, lethargy, difficulty staying awake, seizures, visual impairment, irritability, and tiredness.
Corticosteroids (commonly called steroids), such as dexamethasone (Decadron), are used to treat peritumoral edema. Side effects include high blood pressure, mood swings, increased risk of infection, stronger appetite, facial swelling, and fluid retention.
A shunt procedure may be performed to drain fluid. Shunts are flexible tubes used to reroute and drain the fluid.
Seizures are common in brain tumor cases, with younger patients having higher risks than older ones. Anti-seizure (anti-convulsant) medications, such as carbamazepine or phenobarbital, may treat seizures and are helpful in preventing recurrence. These drugs are not useful in preventing a first seizure, however, and they should not be used routinely to treat patients with newly diagnosed brain tumors. Anti-seizure medications should be used only for patients who have experienced a seizure.
Anti-seizure medications can interact with some of the chemotherapies used to treat brain cancers, including paclitaxel, irinotecan, interferon, and retinoic acid. Patients should discuss these interactions with their doctors.
Physical and occupational therapists can assist with rehabilitation for muscle weakness and speech problems. They can also advise on home modifications, assistive devices, and adaptive tools.
Patients should discuss emotional as well as physical issues with their doctors. Depression can be treated medically and through psychotherapy. Relaxation techniques can be helpful. Support groups can also have great benefit for both patients and families.
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Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.