Pineal Gland Parenchymal Tumor

  • Dana-Farber/Brigham and Women's Cancer Care

    A pineal parenchymal tumor forms in parenchymal cells or pineocytes, which are the cells that make up most of the pineal gland (a tiny organ in the cerebrum that produces melatonin). Learn about pineal gland parenchymal tumors and find information on how we support and care for people with pineal gland parenchymal tumors before, during, and after treatment.

Treatment 

The Center for Neuro-Oncology offers state-of the-art treatments for patients with brain tumors, spinal cord tumors, and neurologic complications from cancer.

We specialize in services for patients with benign or malignant tumors, including:

  • Brain tumors: high-grade glioma, astrocytoma, oligodendroglioma, anaplastic glioma, glioblastoma, medulloblastoma, and meningioma
  • Pituitary, acoustic and skull base tumors: chordoma, meningioma, acoustic neuroma, hemangioblastoma, and pituitary adenoma

Our clinicians are experts in precise neurosurgical techniques, radiation therapy that targets tumors while sparing surrounding tissues, and a variety of chemotherapy and molecular drugs targeting your type of cancer.

Our approach to compassionate care centers on the needs of our patients and their families. Our specialists work as a team to ensure that you receive carefully coordinated treatment and support. We focus on helping you cope with your illness and maintain the quality of your life.

Our research program is a leader in clinical trials for brain tumors. Our goal is to bring laboratory discoveries directly to patients, allowing us to offer new treatment options. We offer our patients access to a range of clinical trials for various types and stages of brain and spinal cord cancers.

We believe that you and your family are key members of the care team. While we understand your illness, you understand your own body. We welcome your questions and value your participation as we make decisions together.

Learn more about treatment for brain tumors in the Center for Neuro-oncology 

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women's Cancer Center, please call 877-442-3324 or use this online form to request an appointment.

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Referring physicians: 617-632-3703 

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Information for: Patients | Healthcare Professionals

General Information About Adult Brain Tumors

An adult brain tumor is a disease in which abnormal cells form in the tissues of the brain.

There are many types of brain and spinal cordtumors. The tumors are formed by the abnormal growth of cells and may begin in different parts of the brain or spinal cord. Together, the brain and spinal cord make up the central nervous system (CNS).

The tumors may be either benign (not cancer) or malignant (cancer):

  • Benign brain and spinal cord tumors grow and press on nearby areas of the brain. They rarely spread into other tissues and may recur (come back).
  • Malignant brain and spinal cord tumors are likely to grow quickly and spread into other brain tissue.

When a tumor grows into or presses on an area of the brain, it may stop that part of the brain from working the way it should. Both benign and malignant brain tumors cause signs and symptoms and need treatment.

Brain and spinal cord tumors can occur in both adults and children. However, treatment for children may be different than treatment for adults. (See the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview for more information on the treatment of children.)

For information about lymphoma that begins in the brain, see the PDQ summary on Primary CNS Lymphoma Treatment.

A brain tumor that starts in another part of the body and spreads to the brain is called a metastatic tumor.

Tumors that start in the brain are called primary brain tumors. Primary brain tumors may spread to other parts of the brain or to the spine. They rarely spread to other parts of the body.

Often, tumors found in the brain have started somewhere else in the body and spread to one or more parts of the brain. These are called metastatic brain tumors (or brain metastases). Metastatic brain tumors are more common than primary brain tumors.

About half of metastatic brain tumors are from lung cancer. Other types of cancer that commonly spread to the brain are melanoma and cancer of the breast, colon, kidney, nasopharynx, and unknown primary site. Leukemia, lymphoma, breast cancer, and gastrointestinal cancer may spread to the leptomeninges (the two innermost membranes covering the brain and spinal cord). This is called leptomeningeal carcinomatosis.

See the following for more information from PDQ about cancers that commonly spread to the brain or spinal cord:

  • Adult Hodgkin Lymphoma Treatment
  • Adult Non-Hodgkin Lymphoma Treatment
  • Breast Cancer Treatment
  • Carcinoma of Unknown Primary Treatment
  • Colon Cancer Treatment
  • Leukemia Home Page 
  • Melanoma Treatment
  • Nasopharyngeal Cancer Treatment
  • Non-Small Cell Lung Cancer Treatment
  • Renal Cell Cancer Treatment
  • Small Cell Lung Cancer Treatment

The brain controls many important body functions.

The brain has three major parts:

  • The cerebrum is the largest part of the brain. It is at the top of the head. The cerebrum controls thinking, learning, problem solving, emotions, speech, reading, writing, and voluntary movement.
  • The cerebellum is in the lower back of the brain (near the middle of the back of the head). It controls movement, balance, and posture.
  • The brain stem connects the brain to the spinal cord. It is in the lowest part of the brain (just above the back of the neck). The brain stem controls breathing, heart rate, and the nerves and muscles used to see, hear, walk, talk, and eat.
Drawing of brain anatomy showing the brain stem, pons, medulla, spinal cord, cerebellum, cerebrum, meninges, ventricles (fluid-filled spaces), and skull.   Drawing of the inside of the brain showing ventricles (fluid-filled spaces), choroid plexus, hypothalamus, pineal gland, pituitary gland, optic nerve, brain stem, cerebellum, cerebrum, medulla, pons, and spinal cord.  
Anatomy of the brain, showing the cerebrum, cerebellum, brain stem, and other parts of the brain. Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain.

The spinal cord connects the brain to nerves in most parts of the body.

The spinal cord is a column of nerve tissue that runs from the brain stem down the center of the back. It is covered by three thin layers of tissue called membranes. These membranes are surrounded by the vertebrae (back bones). Spinal cord nerves carry messages between the brain and the rest of the body, such as a message from the brain to cause muscles to move or a message from the skin to the brain to feel touch.

There are different types of brain and spinal cord tumors.

Brain and spinal cord tumors are named based on the type of cell they formed in and where the tumor first formed in the CNS. The grade of a tumor may be used to tell the difference between slow-growing and fast-growing types of the tumor. The World Health Organization (WHO) tumor grades are based on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread.

WHO Tumor Grading System

  • Grade I (low-grade) — The tumor grows slowly, has cells that look a lot like normal cells, and rarely spreads into nearby tissues. Grade I brain tumors may be cured if they are completely removed by surgery.
  • Grade II — The tumor grows slowly, but may spread into nearby tissue and may recur (come back). Some tumors may become a higher-grade tumor.
  • Grade III — The tumor grows quickly, is likely to spread into nearby tissue, and the tumor cells look very different from normal cells.
  • Grade IV (high-grade) — The tumor grows and spreads very quickly and the cells do not look like normal cells. There may be areas of dead cells in the tumor. Grade IV tumors usually cannot be cured.

The following types of tumors can form in the brain or spinal cord:

Astrocytic Tumors

An astrocytic tumor begins in star-shaped brain cells called astrocytes, which help keep nerve cells healthy. An astrocyte is a type of glial cell. Glial cells sometimes form tumors called gliomas. Astrocytic tumors include the following:

  • Brain stem glioma (usually high grade): A brain stem glioma forms in the brain stem, which is the part of the brain connected to the spinal cord. It is often a high-grade tumor, which spreads widely through the brain stem and is hard to cure. Brain stem gliomas are rare in adults. (See the PDQ summary on Childhood Brain Stem Glioma Treatment for more information.)
  • Pineal astrocytic tumor (any grade): A pineal astrocytic tumor forms in tissue around the pineal gland and may be any grade. The pineal gland is a tiny organ in the brain that makes melatonin, a hormone that helps control the sleeping and waking cycle.
  • Pilocytic astrocytoma (grade I): A pilocyticastrocytoma grows slowly in the brain or spinal cord. It may be in the form of a cyst and rarely spreads into nearby tissues. Pilocytic astrocytomas can often be cured.
  • Diffuse astrocytoma (grade II): A diffuse astrocytoma grows slowly, but often spreads into nearby tissues. The tumor cells look something like normal cells. In some cases, a diffuse astrocytoma can be cured. It is also called a low-grade diffuse astrocytoma.
  • Anaplastic astrocytoma (grade III): An anaplastic astrocytoma grows quickly and spreads into nearby tissues. The tumor cells look different from normal cells. This type of tumor usually cannot be cured. An anaplastic astrocytoma is also called a malignant astrocytoma or high-grade astrocytoma.
  • Glioblastoma (grade IV): A glioblastoma grows and spreads very quickly. The tumor cells look very different from normal cells. This type of tumor usually cannot be cured. It is also called glioblastoma multiforme.

See the PDQ summary on Childhood Astrocytomas Treatment for more information about astrocytomas in children.

Oligodendroglial Tumors

An oligodendroglial tumor begins in brain cells called oligodendrocytes, which help keep nerve cells healthy. An oligodendrocyte is a type of glial cell. Oligodendrocytes sometimes form tumors called oligodendrogliomas. Grades of oligodendroglial tumors include the following:

  • Oligodendroglioma (grade II): An oligodendroglioma grows slowly, but often spreads into nearby tissues. The tumor cells look something like normal cells. In some cases, an oligodendroglioma can be cured.
  • Anaplastic oligodendroglioma (grade III): An anaplastic oligodendroglioma grows quickly and spreads into nearby tissues. The tumor cells look different from normal cells. This type of tumor usually cannot be cured.

See the PDQ summary on Childhood Astrocytomas Treatment for more information about oligodendroglial tumors in children.

Mixed Gliomas

A mixed glioma is a brain tumor that has two types of tumor cells in it — oligodendrocytes and astrocytes. This type of mixed tumor is called an oligoastrocytoma.

  • Oligoastrocytoma (grade II): An oligoastrocytoma is a slow-growing tumor. The tumor cells look something like normal cells. In some cases, an oligoastrocytoma can be cured.
  • Anaplastic oligoastrocytoma (grade III): An anaplastic oligoastrocytoma grows quickly and spreads into nearby tissues. The tumor cells look different from normal cells. This type of tumor has a worse prognosis than oligoastrocytoma (grade II).

See the PDQ summary on Childhood Astrocytomas Treatment for more information about mixed gliomas in children.

Ependymal Tumors

An ependymal tumor usually begins in cells that line the fluid-filled spaces in the brain and around the spinal cord. An ependymal tumor may also be called an ependymoma. Grades of ependymomas include the following:

  • Ependymoma (grade I or II): A grade I or II ependymoma grows slowly and has cells that look something like normal cells. There are two types of grade I ependymoma — myxopapillary ependymoma and subependymoma. A grade II ependymoma grows in a ventricle (fluid-filled space in the brain) and its connecting paths or in the spinal cord. In some cases, a grade I or II ependymoma can be cured.
  • Anaplastic ependymoma (grade III): An anaplastic ependymoma grows quickly and spreads into nearby tissues. The tumor cells look different from normal cells. This type of tumor usually has a worse prognosis than a grade I or II ependymoma.

See the PDQ summary on Childhood Ependymoma Treatment for more information about ependymoma in children.

Medulloblastomas

A medulloblastoma is a type of embryonal tumor. Medulloblastomas are most common in children or young adults.

See the PDQ summary on Childhood Central Nervous System Embryonal Tumors Treatment for more information about medulloblastomas in children.

Pineal Parenchymal Tumors

A pineal parenchymal tumor forms in parenchymal cells or pineocytes, which are the cells that make up most of the pineal gland. These tumors are different from pineal astrocytic tumors. Grades of pineal parenchymal tumors include the following:

  • Pineocytoma (grade II): A pineocytoma is a slow-growing pineal tumor.
  • Pineoblastoma (grade IV): A pineoblastoma is a rare tumor that is very likely to spread.

See the PDQ summary on Childhood Central Nervous System Embryonal Tumors Treatment for more information about pineal parenchymal tumors in children.

Meningeal Tumors

A meningeal tumor, also called a meningioma, forms in the meninges (thin layers of tissue that cover the brain and spinal cord). It can form from different types of brain or spinal cord cells. Meningiomas are most common in adults. Types of meningeal tumors include the following:

  • Meningioma (grade I): A grade I meningioma is the most common type of meningeal tumor. A grade I meningioma is a slow-growing tumor. It forms most often in the dura mater. A grade I meningioma can be cured if it is completely removed by surgery.
  • Meningioma (grade II and III): This is a rare meningeal tumor. It grows quickly and is likely to spread within the brain and spinal cord. The prognosis is worse than a grade I meningioma because the tumor usually cannot be completely removed by surgery.

A hemangiopericytoma is not a meningeal tumor but is treated like a grade II or III meningioma. A hemangiopericytoma usually forms in the dura mater. The prognosis is worse than a grade I meningioma because the tumor usually cannot be completely removed by surgery.

Germ Cell Tumors

A germ cell tumor forms in germ cells, which are the cells that develop into sperm in men or ova (eggs) in women. There are different types of germ cell tumors. These include germinomas, teratomas, embryonal yolk sac carcinomas, and choriocarcinomas. Germ cell tumors can be either benign or malignant.

See the PDQ summary on Childhood Central Nervous System Germ Cell Tumors Treatment for more information about childhood germ cell tumors in the brain.

Craniopharyngioma (Grade I)

A craniopharyngioma is a rare tumor that usually forms just above the pituitary gland (a pea-sized organ at the bottom of the brain that controls other glands). Craniopharyngiomas can form from different types of brain or spinal cord cells. They begin in the center of the brain, just above the back of the nose.

See the PDQ summary on Childhood Craniopharyngioma Treatment for more information about craniopharyngioma in children.

Recurrent Brain Tumors

A recurrent brain tumor is a tumor that has recurred (come back) after it has been treated. Brain tumors often recur, sometimes many years after the first tumor. The tumor may recur at the same place in the brain or in other parts of the central nervous system.

Having certain genetic syndromes may affect the risk of a brain tumor.

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. There are few known risk factors for brain tumors. The following conditions may increase the risk of certain types of brain tumors:

  • Being exposed to vinyl chloride may increase the risk of glioma.
  • Infection with the Epstein-Barr virus, having AIDS (acquired immunodeficiency syndrome), or receiving an organ transplant may increase the risk of primary CNS lymphoma. (See the PDQ summary on Primary CNS Lymphoma for more information.)
  • Having certain geneticsyndromes may increase the risk brain tumors:
    • Neurofibromatosis type 1 (NF1) or 2 (NF2).
    • von Hippel-Lindau disease.
    • Tuberous sclerosis.
    • Li-Fraumeni syndrome.
    • Turcot syndrome type 1 or 2.
    • Nevoid basal cell carcinoma syndrome.
     

The cause of most adult brain and spinal cord tumors is unknown.

The signs and symptoms of adult brain and spinal cord tumors are not the same in every person.

Signs and symptoms depend on the following:

  • Where the tumor forms in the brain.
  • What the affected part of the brain controls.
  • The size of the tumor.

Signs and symptoms may be caused by brain tumors or by other conditions, including cancer that has spread to the brain. Check with your doctor if you have any of the following:

Brain Tumors

  • Morning headache or headache that goes away after vomiting.
  • Frequent nausea and vomiting.
  • Loss of appetite.
  • Vision, hearing, and speech problems.
  • Loss of balance and trouble walking.
  • Weakness.
  • Unusual sleepiness or change in activity level.
  • Changes in personality, mood, ability to focus, or behavior.
  • Seizures.

Spinal Cord Tumors

  • Back pain or pain that spreads from the back towards the arms or legs.
  • A change in bowel habits or trouble urinating.
  • Weakness in the legs.
  • Trouble walking.

Tests that examine the brain and spinal cord are used to diagnose adult brain and spinal cord tumors.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
  • Visual field exam: An exam to check a person’s field of vision (the total area in which objects can be seen). This test measures both central vision (how much a person can see when looking straight ahead) and peripheral vision (how much a person can see in all other directions while staring straight ahead). Any loss of vision may be a sign of a tumor that has damaged or pressed on the parts of the brain that affect eyesight.
  • Tumor marker test: A procedure in which a sample of blood, urine, or tissue is checked to measure the amounts of certain substances made by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the body. These are called tumor markers. This test may be done to diagnose a germ cell tumor.
  • Gene testing: A laboratory test in which a sample of blood or tissue is tested for changes in a chromosome that has been linked with a certain type of brain tumor. This test may be done to diagnose an inherited syndrome.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of the brain and spinal cord. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI). Sometimes a procedure called magnetic resonance spectroscopy (MRS) is done during the MRI scan. An MRS is used to diagnose tumors, based on their chemical make-up. MRI is often used to diagnose tumors in the spinal cord.
  • SPECT scan (single photon emission computed tomography scan): A procedure that uses a special camera linked to a computer to make a 3-dimensional (3-D) picture of the brain. A small amount of a radioactive substance is injected into a vein or inhaled through the nose. As the substance travels through the blood, the camera rotates around the head and takes pictures of the brain. Blood flow and metabolism are higher than normal in areas where cancer cells are growing. These areas will show up brighter in the picture. This procedure may be done just before or after a CT scan. SPECT is used to tell the difference between a primary tumor and a tumor that has spread to the brain from somewhere else in the body.
  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the brain. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. PET is used to tell the difference between a primary tumor and a tumor that has spread to the brain from somewhere else in the body.
  • Angiogram: A procedure to look at blood vessels and the flow of blood in the brain. A contrast dye is injected into the blood vessel. As the contrast dye moves through the blood vessel, x-rays are taken to see if the vessel is blocked.

A biopsy is also used to diagnose a brain tumor.

If imaging tests show there may be a brain tumor, a biopsy is usually done. One of the following types of biopsies may be used:

  • Stereotactic biopsy: When imaging tests show there may be a tumor deep in the brain in a hard to reach place, a stereotactic brain biopsy may be done. This kind of biopsy uses a computer and a 3-dimensional scanning device to find the tumor and guide the needle used to remove the tissue. A small incision is made in the scalp and a small hole is drilled through the skull. A biopsy needle is inserted through the hole to remove cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
  • Open biopsy: When imaging tests show that there may be a tumor that can be removed by surgery, an open biopsy may be done. A part of the skull is removed in an operation called a craniotomy. A sample of brain tissue is removed and viewed under a microscope by a pathologist. If cancer cells are found, some or all of the tumor may be removed during the same surgery. Tests are done before surgery to find the areas around the tumor that are important for normal brain function. There are also ways to test brain function during surgery. The doctor will use the results of these tests to remove as much of the tumor as possible with the least damage to normal tissue in the brain.
    Drawing of a craniotomy showing a section of the scalp that has been pulled back to remove a piece of the skull; the dura covering the brain has been opened to expose the brain. The layer of muscle under the scalp is also shown. 
    Craniotomy: An opening is made in the skull and a piece of the skull is removed to show part of the brain.

The pathologist checks the biopsy sample to find out the type and grade of brain tumor. The grade of the tumor is based on how the tumor cells look under a microscope and how quickly the tumor is likely to grow and spread.

The following tests may be done on the tumor tissue that is removed:

  • Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer.
  • Light and electron microscopy: A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
  • Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.

Sometimes a biopsy or surgery cannot be done.

For some tumors, a biopsy or surgery cannot be done safely because of where the tumor formed in the brain or spinal cord. These tumors are diagnosed and treated based on the results of imaging tests and other procedures.

Sometimes the results of imaging tests and other procedures show that the tumor is very likely to be benign and a biopsy is not done.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options for primary brain and spinal cord tumors depend on the following:

  • The type and grade of the tumor.
  • Where the tumor is in the brain or spinal cord.
  • Whether the tumor can be removed by surgery.
  • Whether cancer cells remain after surgery.
  • Whether there are certain changes in the chromosomes.
  • Whether the cancer has just been diagnosed or has recurred (come back).
  • The patient's general health.

The prognosis and treatment options for metastatic brain and spinal cord tumors depend on the following:

  • Whether there are more than two tumors in the brain or spinal cord.
  • Where the tumor is in the brain or spinal cord.
  • How well the tumor responds to treatment.
  • Whether the primary tumor continues to grow or spread.

Stages of Adult Brain Tumors

There is no standard staging system for adult brain and spinal cord tumors.

The extent or spread of cancer is usually described as stages. There is no standard staging system for brain and spinal cordtumors. Brain tumors that begin in the brain may spread to other parts of the brain and spinal cord, but they rarely spread to other parts of the body. Treatment of brain and spinal cord tumors is based the following:

  • The type of cell in which the tumor began.
  • Where the tumor formed in the brain or spinal cord.
  • The amount of cancer left after surgery.
  • The grade of the tumor.

Treatment of brain tumors that have spread to the brain from other parts of the body is based on the number of tumors in the brain.

Imaging tests may be repeated after surgery to help plan more treatment.

Some of the tests and procedures used to diagnose a brain or spinal cord tumor may be repeated after treatment to find out how much tumor is left.

Treatment Option Overview

There are different types of treatment for patients with adult brain and spinal cord tumors.

Different types of treatment are available for patients with adult brain and spinal cordtumors. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change.

Surgery

Surgery may be used to diagnose and treat adult brain and spinal cord tumors. See the General Information section of this summary.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type of tumor and where it is in the brain or spinal cord.

The following ways of giving radiation therapy to the tumor cause less damage to the healthy tissue that is around the tumor:

  • 3-dimensional conformal radiation therapy: A procedure that uses a computer to create a 3-dimensional (3-D) picture of the brain or spinal cord tumor. This allows doctors to give the highest possible dose of radiation to the tumor, with as little damage to normal tissue as possible. This type of radiation therapy is also called 3-dimensional radiation therapy and 3D-CRT.
  • Intensity-modulated radiation therapy (IMRT): A type of 3-D radiation therapy that uses a computer to make pictures of the size and shape of the brain or spinal cord tumor. Thin beams of radiation of different intensities (strengths) are aimed at the tumor from many angles. This type of radiation therapy causes less damage to healthy tissue near the tumor.
  • Stereotactic radiosurgery: A type of radiation therapy that uses a head frame attached to the skull to aim a single large dose of radiation directly to a brain tumor. This causes less damage to nearby healthy tissue. Stereotactic radiosurgery is also called stereotaxic radiosurgery, radiosurgery, and radiation surgery. This procedure does not involve surgery.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. To treat brain tumors, a wafer that dissolves may be used to deliver an anticancer drug directly to the brain tumor site after the tumor has been removed by surgery. The way the chemotherapy is given depends on the type of tumor and where it is in the brain.

Anticancer drugs given by mouth or vein to treat brain and spinal cord tumors cannot cross the blood-brain barrier and enter the fluid that surrounds the brain and spinal cord. Instead, an anticancer drug is injected into the fluid-filled space to kill cancer cells there. This is called intrathecal chemotherapy.

See Drugs Approved for Brain Tumors for more information.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Monoclonal antibodytherapy is a type of targeted therapy that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

Bevacizumab is a monoclonal antibody that binds to a protein called vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. Bevacizumab is used in the treatment of recurrentglioblastoma.

Other types of targeted therapies are being studied for adult brain tumors, including tyrosine kinase inhibitors.

See Drugs Approved for Brain Tumors for more information.

New types of treatment are being tested in clinical trials.

This summary section refers to new treatments being studied in clinical trials, but it may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Proton beam radiation therapy

Proton beam radiation therapy is a type of high-energy, external radiation therapy that uses streams of protons (small, positively-charged pieces of matter) to make radiation. This type of radiation kills tumor cells with little damage to nearby tissues. It is used to treat cancers of the head, neck, and spine and organs such as the brain, eye, lung, and prostate. Proton beam radiation is different from x-ray radiation.

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Biologic therapy is being studied for the treatment of some types of brain tumors. Treatments may include the following:

  • Dendritic cell vaccine therapy.
  • Gene therapy.

Supportive care is given to lessen the problems caused by the disease or its treatment.

This therapy controls problems or side effects caused by the disease or its treatment and improves quality of life. For brain tumors, supportive care includes drugs to control seizures and fluid buildup or swelling in the brain.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

The following tests and procedures may be used to check whether a brain tumor has come back after treatment:

  • SPECT scan (single photon emission computed tomography scan): A procedure that uses a special camera linked to a computer to make a 3-dimensional (3-D) picture of the brain. A small amount of a radioactive substance is injected into a vein or inhaled through the nose. As the substance travels through the blood, the camera rotates around the head and takes pictures of the brain. Blood flow and metabolism are higher than normal in areas where cancer cells are growing. These areas will show up brighter in the picture. This procedure may be done just before or after a CT scan.
  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the brain. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

Treatment Options by Type of Adult Brain Tumor

Astrocytic Tumors

Brain Stem Gliomas

Treatment of brain stem gliomas may include the following:

  • Radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain stem glioma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Pineal Astrocytic Tumors

Treatment of pinealastrocytictumors may include the following:

  • Surgery and radiation therapy. For high-grade tumors, chemotherapy may also be given.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult pineal gland astrocytoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Pilocytic Astrocytomas

Treatment of pilocyticastrocytomas may include the following:

  • Surgery to remove the tumor. Radiation therapy may also be given if tumor remains after surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult pilocytic astrocytoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Diffuse Astrocytomas

Treatment of diffuseastrocytomas may include the following:

  • Surgery with or without radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult diffuse astrocytoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Anaplastic Astrocytomas

Treatment of anaplasticastrocytomas may include the following:

  • Surgery and radiation therapy. Chemotherapy may also be given.
  • A clinical trial of chemotherapy placed into the brain during surgery.
  • A clinical trial of a new treatment added to standard treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult anaplastic astrocytoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Glioblastomas

Treatment of glioblastomas may include the following:

  • Surgery followed by radiation therapy and chemotherapy given at the same time, followed by chemotherapy alone.
  • Chemotherapy placed into the brain during surgery.
  • A clinical trial of a new treatment added to standard treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult glioblastoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Oligodendroglial Tumors

Treatment of oligodendrogliomas may include the following:

  • Surgery with or without radiation therapy. Chemotherapy may also be given.

Treatment of anaplastic oligodendroglioma may include the following:

  • Surgery followed by radiation therapy and/or chemotherapy.
  • A clinical trial of a new treatment added to standard treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult oligodendroglial tumors. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Mixed Gliomas

Treatment of mixed gliomas may include the following:

  • Surgery and radiation therapy. Sometimes chemotherapy is also given.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult mixed glioma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Ependymal Tumors

Treatment of grade I and grade II ependymomas may include the following:

  • Surgery to remove the tumor. Radiation therapy may also be given if tumor remains after surgery.

Treatment of grade III anaplastic ependymoma may include the following:

  • Surgery and radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult ependymal tumors. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Medulloblastomas

Treatment of medulloblastomas may include the following:

  • Surgery and radiation therapy to the brain and spine.
  • A clinical trial of chemotherapy added to surgery and radiation therapy to the brain and spine

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult medulloblastoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Pineal Parenchymal Tumors

Treatment of pinealparenchymaltumors may include the following:

  • For pineocytomas, surgery and radiation therapy.
  • For pineoblastomas, surgery, radiation therapy, and chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult pineal parenchymal tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Meningeal Tumors

Treatment of grade I meningiomas may include the following:

  • Watchful waiting for tumors with no signs or symptoms.
  • Surgery to remove the tumor. Radiation therapy may also be given if tumor remains after surgery.
  • Stereotactic radiosurgery for tumors smaller than 3 centimeters.
  • Radiation therapy for tumors that cannot be removed by surgery.

Treatment of grade II and III meningioma and hemangiopericytoma may include the following:

  • Surgery and radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult meningeal tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Germ Cell Tumors

There is no standard treatment for germ cell tumors (germinoma, embryonal carcinoma, choriocarcinoma, and teratoma). Treatment depends on what the tumorcells look like under a microscope, the tumor markers, where the tumor is in the brain, and whether it can be removed by surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult central nervous system germ cell tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Craniopharyngiomas

Treatment of craniopharyngiomas may include the following:

  • Surgery to completely remove the tumor.
  • Surgery to remove as much of the tumor as possible, followed by radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult craniopharyngioma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Recurrent Brain Tumors

There is no standard treatment for recurrentbrain tumors. Treatment depends on the patient's condition, the expected side effects of the treatment, where the tumor is in the brain, and whether the tumor can be removed by surgery. Treatment may include the following:

  • Surgery to remove the tumor.
  • Chemotherapy with drugs not used to treat the original tumor.
  • Chemotherapy placed into the brain during surgery.
  • Radiation therapy.
  • Targeted therapy for recurrent glioblastoma.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult brain tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Metastatic Brain Tumors

Treatment of a single tumor that has spread to the brain from another part of the body may include the following:

  • Radiation therapy to the whole brain.
  • Stereotactic radiosurgery followed by radiation therapy to the whole brain.
  • Surgery followed by radiation therapy to the whole brain. It is not known if surgery improves survival.

Treatment of more than one tumor that has spread to the brain from another part of the body may include the following:

  • Radiation therapy to the whole brain.
  • Stereotactic radiosurgery.
  • Radiation therapy to the whole brain and stereotactic radiosurgery.
  • Chemotherapy, if the primary tumor is one that responds to anticancerdrugs.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with tumors metastatic to brain. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Spinal Cord Tumors

Treatment of spinal cordtumors may include the following:

  • Surgery to remove the tumor.
  • Radiation therapy.
  • Chemotherapy (systemic and/or intrathecal), if the tumor has spread to the leptomeninges (leptomeningeal carcinomatosis). Radiation therapy may also be given.
  • Supportive care may be given for leptomeningeal carcinomatosis.
  • A clinical trial of a new treatment.

To Learn More About Adult Brain Tumors

For more information from the National Cancer Institute about adult brain tumors, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on September 2, 2014.


General Information About Adult Brain Tumors

Incidence and Mortality

Estimated new cases and deaths from brain and other nervous system tumors in the United States in 2014:[1]

  • New cases: 23,380.
  • Deaths: 14,320.

Brain tumors account for 85% to 90% of all primary central nervous system (CNS) tumors.[2] Available registry data from the Surveillance, Epidemiology, and End Results (SEER) database for 2007 indicate that the combined incidence of primary invasive CNS tumors in the United States is 6.36 per 100,000 persons per year with an estimated mortality of 4.22 per 100,000 persons per year.[3] Worldwide, approximately 238,000 new cases of brain and other CNS tumors were diagnosed in the year 2008, with an estimated 175,000 deaths.[4] In general, the incidence of primary brain tumors is higher in whites than in blacks, and mortality is higher in males than in females.[2]

Risk Factors

Few definitive observations on environmental or occupational causes of primary CNS tumors have been made.[2] Exposure to vinyl chloride may predispose to the development of glioma. Epstein-Barr virus infection has been implicated in the etiology of primary CNS lymphoma. Transplant recipients and patients with the acquired immunodeficiency syndrome have substantially increased risks for primary CNS lymphoma.[2][5] (Refer to the PDQ summary on Primary CNS Lymphoma Treatment for more information.)

Disease Overview

The glial cell tumors, anaplastic astrocytoma and glioblastoma, account for approximately 38% of primary brain tumors. Since anaplastic astrocytomas represent less than 10% of all CNS gliomas, phase III randomized trials restricted to the anaplastic astrocytomas are not practical. Meningiomas and other mesenchymal tumors account for approximately 27% of primary brain tumors.[2]

Other less-common primary brain tumors include the following in decreasing order of frequency:

  • Pituitary tumors.
  • Schwannomas.
  • CNS lymphomas.
  • Oligodendrogliomas.
  • Ependymomas.
  • Low-grade astrocytomas.
  • Medulloblastomas.

Schwannomas, meningiomas, and ependymomas account for up to 79% of primary spinal tumors. Other less common primary spinal tumors include sarcomas, astrocytomas, vascular tumors, and chordomas, in decreasing order of frequency. The familial tumor syndromes (and respective chromosomal abnormalities that are associated with CNS neoplasms) include neurofibromatosis type I (17q11), neurofibromatosis type II (22q12), von Hippel-Lindau disease (3p25-26), tuberous sclerosis (9q34, 16p13), Li-Fraumeni syndrome (17p13), Turcot syndrome type 1 (3p21, 7p22), Turcot syndrome type 2 (5q21), and nevoid basal cell carcinoma syndrome (9q22.3).[6][7]

Clinical Presentation

The clinical presentation of various brain tumors is best appreciated by considering the relationship of signs and symptoms to anatomy.[2] General signs and symptoms include the following:

  • Headaches.
  • Seizures.
  • Visual changes.
  • Gastrointestinal symptoms such as nausea, loss of appetite, and vomiting.
  • Changes in personality, mood, mental capacity, and concentration.

Whether primary, metastatic, malignant, or benign, brain tumors must be differentiated from other space-occupying lesions such as abscesses, arteriovenous malformations, and infarction, which can have a similar clinical presentation.[8] Other clinical presentations of brain tumors include focal cerebral syndromes such as seizures.[2] Seizures are a presenting symptom in approximately 20% of patients with supratentorial brain tumors and may antedate the clinical diagnosis by months to years in patients with slow-growing tumors. Among all patients with brain tumors, 70% with primary parenchymal tumors and 40% with metastatic brain tumors develop seizures at some time during the clinical course.[9]

Diagnosis

Testing

Computed tomography (CT) and magnetic resonance imaging (MRI) have complementary roles in the diagnosis of CNS neoplasms.[8][10] The speed of CT is desirable for evaluating clinically unstable patients. CT is superior for detecting calcification, skull lesions, and hyperacute hemorrhage (bleeding less than 24-hours old) and helps direct differential diagnosis as well as immediate management. MRI has superior soft-tissue resolution. MRI can better detect isodense lesions, tumor enhancement, and associated findings such as edema, all phases of hemorrhagic states (except hyperacute), and infarction. High-quality MRI is the diagnostic study of choice in the evaluation of intramedullary and extramedullary spinal cord lesions.[2] In posttherapy imaging, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) may be useful in differentiating tumor recurrence from radiation necrosis.[8]

Biopsy confirmation to corroborate the suspected diagnosis of a primary brain tumor is critical, whether before surgery by needle biopsy or at the time of surgical resection, except in cases in which the clinical and radiologic picture clearly point to a benign tumor. Radiologic patterns may be misleading, and a definitive biopsy is needed to rule out other causes of space-occupying lesions, such as metastatic cancer or infection. CT- or MRI-guided stereotactic techniques can be used to place a needle safely and accurately into all but a very few inaccessible locations within the brain.

CNS abnormalities

Specific genetic or chromosomal abnormalities involving deletions of 1p and 19q have been identified for a subset of oligodendroglial tumors, which have a high response rate to chemotherapy.[2][7][11][12][13][14][15] Other CNS tumors are associated with characteristic patterns of altered oncogenes, altered tumor-suppressor genes, and chromosomal abnormalities. Familial tumor syndromes with defined chromosomal abnormalities are associated with gliomas. (Refer to the Classification section of this summary for more information.)

Metastatic Brain Tumors

Brain metastases outnumber primary neoplasms by at least 10 to 1, and they occur in 20% to 40% of cancer patients.[16] Because no national cancer registry documents brain metastases, the exact incidence is unknown, but it has been estimated that 98,000 to 170,000 new cases are diagnosed in the United States each year.[2][8] This number may be increasing because of the capacity of MRI to detect small metastases and because of prolonged survival resulting from improved systemic therapy.[2][16]

Origins of metastatic brain tumors

The most common primary cancers metastasizing to the brain are lung cancer (50%), breast cancer (15%–20%), unknown primary cancer (10%–15%), melanoma (10%), and colon cancer (5%).[2][16] Eighty percent of brain metastases occur in the cerebral hemispheres, 15% occur in the cerebellum, and 5% occur in the brain stem.[2] Metastases to the brain are multiple in more than 70% of cases, but solitary metastases also occur.[16] Brain involvement can occur with cancers of the nasopharyngeal region by direct extension along the cranial nerves or through the foramina at the base of the skull. Dural metastases may constitute as much as 9% of total CNS metastases.

Primary Brain Tumors

A lesion in the brain should not be assumed to be a metastasis just because a patient has had a previous cancer; such an assumption could result in overlooking appropriate treatment of a curable tumor. Primary brain tumors rarely spread to other areas of the body, but they can spread to other parts of the brain and to the spinal axis.

Clinical Features

The diagnosis of brain metastases in cancer patients is based on the following:

  • Patient history.
  • Neurological examination.
  • Diagnostic procedures, including a contrast MRI of the brain.

Patients may describe any of the following:

  • Headaches.
  • Weakness.
  • Seizures.
  • Sensory defects.
  • Gait problems.

Often, family members or friends may notice the following:

  • Lethargy.
  • Emotional lability.
  • Personality change.

A physical examination may show objective neurological findings or only minor cognitive changes. The presence of multiple lesions and a high predilection of primary tumor metastasis may be sufficient to make the diagnosis of brain metastasis. In the case of a solitary lesion or a questionable relationship to the primary tumor, a brain biopsy (via resection or stereotactic biopsy) may be necessary. CT scans with contrast or MRIs with gadolinium are quite sensitive in diagnosing the presence of metastases. PET scanning and spectroscopic evaluation are new strategies to diagnose cerebral metastases and to differentiate the metastases from other intracranial lesions.[17]

Related Summaries

Other PDQ summaries containing information related to adult and childhood brain cancer include the following:

  • Breast Cancer Treatment
  • Childhood Brain and Spinal Cord Tumors Treatment Overview
  • Colon Cancer Treatment
  • Non-Small Cell Lung Cancer Treatment
  • Small Cell Lung Cancer Treatment
  • Testicular Cancer Treatment

References:

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.

  2. Mehta M, Vogelbaum MA, Chang S, et al.: Neoplasms of the central nervous system. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1700-49.

  3. Altekruse SF, Kosary CL, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2007. Bethesda, Md: National Cancer Institute, 2010. Also available online. Last accessed May 21, 2014.

  4. Ferlay J, Shin HR, Bray F, et al.: GLOBOCAN 2008: Cancer Incidence and Mortality Worldwide in 2008. Lyon, France: IARC CancerBase No. 10. Available online. Last accessed July 2, 2014.

  5. Schabet M: Epidemiology of primary CNS lymphoma. J Neurooncol 43 (3): 199-201, 1999.

  6. Behin A, Hoang-Xuan K, Carpentier AF, et al.: Primary brain tumours in adults. Lancet 361 (9354): 323-31, 2003.

  7. Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.

  8. Hutter A, Schwetye KE, Bierhals AJ, et al.: Brain neoplasms: epidemiology, diagnosis, and prospects for cost-effective imaging. Neuroimaging Clin N Am 13 (2): 237-50, x-xi, 2003.

  9. Cloughesy T, Selch MT, Liau L: Brain. In: Haskell CM: Cancer Treatment. 5th ed. Philadelphia, Pa: WB Saunders Co, 2001, pp 1106-42.

  10. Ricci PE: Imaging of adult brain tumors. Neuroimaging Clin N Am 9 (4): 651-69, 1999.

  11. Buckner JC: Factors influencing survival in high-grade gliomas. Semin Oncol 30 (6 Suppl 19): 10-4, 2003.

  12. DeAngelis LM: Brain tumors. N Engl J Med 344 (2): 114-23, 2001.

  13. Ueki K, Nishikawa R, Nakazato Y, et al.: Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors. Clin Cancer Res 8 (1): 196-201, 2002.

  14. Giordana MT, Ghimenti C, Leonardo E, et al.: Molecular genetic study of a metastatic oligodendroglioma. J Neurooncol 66 (3): 265-71, 2004.

  15. Hoang-Xuan K, Capelle L, Kujas M, et al.: Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 22 (15): 3133-8, 2004.

  16. Patchell RA: The management of brain metastases. Cancer Treat Rev 29 (6): 533-40, 2003.

  17. Schaefer PW, Budzik RF Jr, Gonzalez RG: Imaging of cerebral metastases. Neurosurg Clin N Am 7 (3): 393-423, 1996.

Classification of Adult Brain Tumors

This classification is based on the World Health Organization (WHO) classification of central nervous system (CNS) tumors.[1] The WHO approach incorporates and interrelates morphology, cytogenetics, molecular genetics, and immunologic markers in an attempt to construct a cellular classification that is universally applicable and prognostically valid. Earlier attempts to develop a TNM-based classification were dropped: tumor size (T) is less relevant than tumor histology and location, nodal status (N) does not apply because the brain and spinal cord have no lymphatics, and metastatic spread (M) rarely applies because most patients with CNS neoplasms do not live long enough to develop metastatic disease.[2]

The WHO grading of CNS tumors establishes a malignancy scale based on histologic features of the tumor.[3] The histologic grades are as follows:

WHO grade I includes lesions with low proliferative potential, a frequently discrete nature, and the possibility of cure following surgical resection alone.

WHO grade II includes lesions that are generally infiltrating and low in mitotic activity but recur more frequently than grade I malignant tumors after local therapy. Some tumor types tend to progress to higher grades of malignancy.

WHO grade III includes lesions with histologic evidence of malignancy, including nuclear atypia and increased mitotic activity. These lesions have anaplastic histology and infiltrative capacity. They are usually treated with aggressive adjuvant therapy.

WHO grade IV includes lesions that are mitotically active, necrosis-prone, and generally associated with a rapid preoperative and postoperative progression and fatal outcomes. The lesions are usually treated with aggressive adjuvant therapy.

The following table is from the WHO Classification of Tumours of the Central Nervous System and lists the tumor types and grades.[4] Tumors limited to the peripheral nervous system are not included. Detailed descriptions of histopathology, grading methods, incidence, and what is known about etiology specific to each tumor type can be found in the WHO classification book.[4]

WHO Grades of CNS Tumorsa

I

II

III

IV

Astrocytic tumors

Subependymal giant cell astrocytoma

X

Pilocytic astrocytoma

X

Pilomyxoid astrocytoma

X

Diffuse astrocytoma

X

Pleomorphic xanthoastrocytoma

X

Anaplastic astrocytoma

X

Glioblastoma

X

Giant cell glioblastoma

X

Gliosarcoma

X

Oligondendroglial tumors

Oligodendroglioma

X

Anaplastic oligodendroglioma

X

Oligoastrocytic tumors

Oligoastrocytoma

X

Anaplastic oligoastrocytoma

X

Ependymal tumors

Subependymoma

X

Myxopapillary ependymoma

X

Ependymoma

X

Anaplastic ependymoma

X

Choroid plexus tumors

Choroid plexus papilloma

X

Atypical choroid plexus papilloma

X

Choroid plexus carcinoma

X

Other neuroepithelial tumors

Angiocentric glioma

X

Chordoid glioma of the third ventricle

X

Neuronal and mixed neuronal-glial tumors

Gangliocytoma

X

Ganglioglioma

X

Anaplastic ganglioma

X

Desmoplastic infantile astrocytoma and ganglioglioma

X

Dysembryoplastic neuroepithelial tumor

X

Central neurocytoma

X

Extraventricular neurocytoma

X

Cerebellar liponeurocytoma

X

Paraganglioma of the spinal cord

X

Papillary glioneuronal tumor

X

Rosette-forming glioneural tumor of the fourth ventricle

X

Pineal tumors

Pineocytoma

X

Pineal parenchymal tumor of intermediate differentiation

X

X

Pineoblastoma

X

Papillary tumor of the pineal region

X

X

Embryonal tumors

Medulloblastoma

X

CNS primitive neuroectodermal tumor (PNET)

X

Atypical teratoid/rhabdoid tumor

X

Tumors of the cranial and paraspinal nerves

Schwannoma

X

Neurofibroma

X

Perineurioma

X

X

X

Malignant peripheral nerve sheath tumor (MPNST)

X

X

X

Meningeal tumors

Meningioma

X

Atypical meningioma

X

Anaplastic/malignant meningioma

X

Hemangiopericytoma

X

Anaplastic hemangiopericytoma

X

Hemangioblastoma

X

Tumors of the sellar region

Craniopharyngioma

X

Granular cell tumor of the neurohypophysis

X

Pituicytoma

X

Spindle cell oncocytoma of the adenohypophysis

X

a Reprinted with permission from Louis, DN, Ohgaki H, Wiestler, OD, Cavenee, WK. World Health Organization Classification of Tumours of the Nervous System. IARC, Lyon, 2007.

References:

  1. Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.

  2. Brain and spinal cord. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 593-7.

  3. Kleihues P, Burger PC, Scheithauer BW: The new WHO classification of brain tumours. Brain Pathol 3 (3): 255-68, 1993.

  4. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.

Treatment Option Overview

Primary Brain Tumors

Radiation therapy and chemotherapy options vary according to histology and anatomic site of the brain tumor. For glioblastoma, combined modality therapy with resection, radiation, and chemotherapy is standard. Since anaplastic astrocytomas, anaplastic oligodendrogliomas, and anaplastic oligoastrocytomas represent only a small proportion of central nervous system gliomas, phase III randomized trials restricted to them are not generally practical. The natural histories of these tumors are variable, depending on histological and molecular factors; therefore, treatment guidelines are evolving. Therapy involving surgically implanted carmustine-impregnated polymer wafers combined with postoperative external-beam radiation therapy (EBRT) may play a role in the treatment of high-grade gliomas (grade III and IV gliomas) in some patients.[1] Specific treatment options for tumor types are listed below under the tumor types and locations. This section covers general treatment principles.

Dexamethasone, mannitol, and furosemide are used to treat the peritumoral edema associated with brain tumors. Use of anticonvulsants is mandatory for patients with seizures.[2]

Finally, active surveillance is appropriate in some circumstances. With the increasing use of sensitive neuroimaging tools, there has been increased detection of asymptomatic low-grade meningiomas. The majority appear to show minimal growth and can often be safely observed, with therapy deferred until the detection of tumor growth or the development of symptoms.[3][4]

Surgery

For most types of brain tumors in most locations, an attempt at complete or near-complete surgical removal is generally recommended, if possible, within the constraints of preservation of neurologic function and underlying patient health. This recommendation is based on observational evidence that survival is better in patients who undergo tumor resection than in those who have closed biopsy alone.[5][6] However, the benefit of resection has not been tested in randomized trials.

Selection bias can enter into observational studies despite attempts to adjust for patient differences that guide the decision to operate. Therefore, the actual difference in outcome between radical surgery and biopsy alone may not be as large as noted in the retrospective studies.[6] An exception to the general recommendation for attempted resection is the case of deep-seated tumors such as pontine gliomas, which are diagnosed on clinical evidence and treated without initial surgery approximately 50% of the time. In most cases, however, diagnosis by biopsy is preferred. Stereotactic biopsy can be used for lesions that are difficult to reach and resect.

Two primary goals of surgery include:[2]

  1. Establishing a histologic diagnosis.
  2. Reducing intracranial pressure by removing as much tumor as is safely possible to preserve neurological function.

However, total elimination of primary malignant intraparenchymal tumors by surgery alone is rarely achievable. Therefore, intraoperative techniques have been developed to reach a balance between removing as much tumor as is practical and the preservation of functional status. For example, craniotomies with stereotactic resections of primary gliomas can be done in cooperative patients while they are awake, with real-time assessment of neurologic function.[7] Resection proceeds until either the magnetic resonance imaging (MRI) signal abnormality being used to monitor the extent of surgery is completely removed or subtle neurologic dysfunction appears (e.g., slight decrease in rapid alternating motor movement or anomia). Likewise, when the tumor is located in or near language centers in the cortex, intraoperative language mapping can be performed by electrode discharge-induced speech arrest while the patient is asked to count or read.[8]

As is the case with several other specialized operations [9][10] in which postoperative mortality has been associated with the number of procedures performed, postoperative mortality after surgery for primary brain tumors may be associated with hospital and/or surgeon volume.[11] Using the Nationwide Inpatient Sample hospital discharge database for the years 1988 to 2000, which represented 20% of inpatient admissions to nonfederal U.S. hospitals, investigators found that large-volume hospitals had lower in-hospital mortality rates after craniotomies for primary brain tumors (odds ratio [OR] = 0.75 for a tenfold higher caseload; 95% confidence interval [CI], 0.62–0.90) and after needle biopsies (OR = 0.54; 95% CI, 0.35–0.83). For example, although there was no specific sharp threshold in mortality outcomes between low-volume hospitals and high-volume hospitals, craniotomy-associated in-hospital mortality was 4.5% for hospitals with five or fewer procedures per year and 1.5% for hospitals with at least 42 procedures per year.

In-hospital mortality rates decreased over the study years (perhaps because the proportion of elective nonemergent operations increased from 45% to 57%), but the decrease was more rapid in high-volume hospitals than in low-volume hospitals. High-volume surgeons also had lower in-hospital patient mortality rates after craniotomy (OR= 0.60; 95% CI, 0.45–0.79).[11] As with any study of volume-outcome associations, these results may not be causal because they may be affected by residual confounding factors, such as referral patterns, private insurance, and patient selection, despite multivariable adjustment.

Radiation Therapy

High-grade tumors

Radiation therapy has a major role in the treatment of patients with high-grade gliomas. A systematic review and meta-analysis of five randomized trials (plus one trial with allocation by birth date) comparing postoperative radiation therapy (PORT) with no radiation therapy showed a statistically significant survival advantage with radiation (risk ratio (RR) = 0.81; 95% CI, 0.74–0.88).[12][Level of evidence: 1iiA] Based on a randomized trial comparing 60 Gy (in 30 fractions over 6 weeks) with 45 Gy (in 25 fractions over 4 weeks) that showed superior survival in the first group (12 months vs. 9 months median survival; hazard ratio [HR] = 0.81; 95% CI, 0.66–0.99), 60 Gy is the accepted standard dose of EBRT for malignant gliomas.[13][Level of evidence: 1iiA]

EBRT using either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy is considered an acceptable technique in radiation therapy delivery. Typically 2- to 3-cm margins on the MRI-based volumes (T1-weighted and FLAIR [fluid-attentuated inversion recovery]) to create the planning target volume are used. Dose escalation using radiosurgery has not improved outcomes.

A randomized trial tested radiosurgery as a boost added to standard EBRT, but the trial found no improvement in survival, quality of life, or patterns of relapse compared with EBRT without the boost.[14][15]

For the same theoretical reasons, brachytherapy has been used to deliver high doses of radiation locally to the tumor while sparing normal brain tissue. However, this approach is technically demanding and has fallen out of favor with the advent of the above-mentioned techniques.

Low-grade tumors

The role of immediate PORT for low-grade gliomas (i.e., low-grade astrocytoma, oligodendroglioma, mixed oligoastrocytomas) is not as clear as in the case of high-grade tumors. The European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 311 patients with low-grade gliomas to radiation versus observation in the EORTC-22845 and MRC BR04 trials.[16][17] (On central pathology review, about 25% of the patients on the trial were reported to actually have high-grade tumors.) Most of the control patients received radiation at the time of progression. After a median follow-up of 93 months, median progression-free survival was 5.3 years in the radiation arm versus 3.4 years in the control arm (HR = 0.59; 95% CI, 0.45–0.77).[16][17][Level of evidence: 1iiDiii] However, there was no difference in the overall survival (OS) rate (median survival = 7.4 years vs. 7.2 years; HR = 0.97; 95% CI, 0.71–1.34; P = .87).[16][17][Level of evidence: 1iiA] This was caused by a longer survival after progression in the control arm (3.4 years) than in the radiation arm (1.0 years) (P < .0001). The investigators did not collect reliable quality-of-life measurements, so it is not clear whether the delay in initial relapse in the radiation therapy arm translated into improved function or quality of life.

Repeat radiation therapy (re-irradiation)

Because there are no randomized trials, the role of repeat radiation after disease progression or the development of radiation-induced cancers is also ill defined. The literature is limited to small retrospective case series, which makes interpretation difficult.[18] The decision to use repeat radiation must be made carefully because of the risk of neurocognitive deficits and radiation-induced necrosis. One advantage of radiosurgery is the ability to deliver therapeutic doses to recurrences that may require the re-irradiation of previously irradiated brain tissue beyond tolerable dose limits.

Chemotherapy

Systemic chemotherapy

For many years, the nitrosourea carmustine (BCNU) was the standard chemotherapy added to surgery and radiation for malignant gliomas. This was based upon a randomized trial (RTOG-8302) of 467 patients conducted by the Brain Tumor Study Group that compared four regimens after initial resection, including semustine (methyl-CCNU), radiation therapy, radiation therapy plus carmustine, and radiation therapy plus semustine.[19]

The radiation therapy plus carmustine arm had the best survival rate.[19][Level of evidence: 1iiA] A modest impact on survival using nitrosourea-containing chemotherapy regimens for malignant gliomas was confirmed in a patient-level meta-analysis of 12 randomized trials (combined HR death = 0.85; 95% CI, 0.78–0.91).[20]

However, the oral agent, temozolomide, has since replaced the nitrosoureas as the standard systemic chemotherapy for malignant gliomas based upon a large multicenter trial (NCT00006353) of glioblastoma patients conducted by the EORTC-National Cancer Institute of Canada that showed a survival advantage.[21][22][Level of evidence: 1iiA] (Refer to the Glioblastoma section of the Management of Specific Tumor Types and Locations section of this summary for more information.)

Localized chemotherapy

Because malignant glioma-related deaths are nearly always the result of an inability to control intracranial disease (rather than the result of distant metastases), the concept of delivering high doses of chemotherapy while avoiding systemic toxicity is attractive. A biodegradable carmustine wafer has been developed for that purpose. The wafers contain 3.85% carmustine, and up to eight wafers are implanted into the tumor bed lining at the time of open resection, with an intended total dose of about 7.7 mg per wafer (61.6 mg maximum per patient) over a period of 2 to 3 weeks. Two randomized, placebo-controlled trials of this focal drug-delivery method have shown an OS advantage associated with the carmustine wafers versus radiation therapy alone. Both trials had an upper age limit of 65 years. The first was a small trial closed because of a lack of continued availability of the carmustine wafers after 32 patients with high-grade gliomas had been entered.[23] Although OS was better in the carmustine-wafer group (median 58.1 vs. 39.9 weeks; P = .012), there was an imbalance in the study arms (only 11 of the16 patients in the carmustine-wafer group vs. 16 of the 16 patients in the placebo-wafer group had Grade IV glioblastoma tumors).

The second study was, therefore, more informative.[24][25] It was a multicenter study of 240 patients with primary malignant gliomas, 207 of whom had glioblastoma. At initial surgery, they received the carmustine versus placebo wafers, followed by radiation therapy (55 Gy–60 Gy). Systemic therapy was not allowed until recurrence, except in the case of anaplastic oligodendrogliomas, of which there were nine patients. Unlike the initial trial, patient characteristics were well balanced between the study arms. Median survival in the two groups was 13.8 months versus 11.6 months; P = .017 (HR = 0.73; 95% CI, 0.56–0.96). A systematic review combining both studies estimated a HR for overall mortality of 0.65; 95% CI, 0.48–0.86; P = .003.[26][Level of evidence: 1iA]

Treatment Options Under Clinical Evaluation

Patients who have brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Heavy-particle radiation, such as proton-beam therapy, carries the theoretical advantage of delivering high doses of ionizing radiation to the tumor bed while sparing surrounding brain tissue. The data are preliminary for this investigational technique, and are not widely available.

Novel biologic therapies under clinical evaluation for patients with brain tumors include the following:[27]

  • Dendritic cell vaccination.[28]
  • Tyrosine kinase receptor inhibitors.[29]
  • Farnesyl transferase inhibitors.
  • Viral-based gene therapy.[30][31]
  • Oncolytic viruses.
  • Epidermal growth factor-receptor inhibitors.
  • Vascular endothelial growth factor inhibitors.[27]
  • Other antiangiogenesis agents.

Primary Tumors of the Spinal Axis

Surgery and radiation therapy are the primary modalities used to treat tumors of the spinal axis; therapeutic options vary according to the histology of the tumor.[2] The experience with chemotherapy for primary spinal cord tumors is limited; no reports of controlled clinical trials are available for these types of tumors.[2][32] Chemotherapy is indicated for most patients with leptomeningeal involvement (from a primary or metastatic tumor) and positive cerebrospinal fluid (CSF) cytology.[2] Most patients require treatment with corticosteroids, particularly if they are receiving radiation therapy.

Patients who have spinal axis tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Leptomeningeal carcinomatosis (LC)

The management of LC includes the following:

  • Intrathecal chemotherapy.
  • Intrathecal chemotherapy and systemic chemotherapy.
  • Intrathecal chemotherapy and radiation therapy.
  • Supportive care.

LC occurs in about 5% of all cancer patients. The most common types include breast tumors (35%), lung tumors (24%), and hematologic malignancies (16%). Diagnosis includes a combination of neurospinal axis imaging and CSF cytology. Median OS is in the range of 10 to 12 weeks.

In a series of 149 patients with metastatic non-small cell lung carcinoma, cytologically proven LC, poor performance status, high protein level in the CSF, and a high initial CSF white blood cell count were significant poor prognostic factors for survival.[33] Patients received active treatment including intrathecal chemotherapy, whole-brain radiation therapy (WBRT), or epidermal growth factor receptor-thymidine kinase-1, or underwent a ventriculoperitoneal shunt procedure.

In a retrospective series of 38 patients with metastatic breast cancer and LC, the proportion of luminal A, B, human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer subtype was 18.4%, 31.6%, 26.3% and 23.7%, respectively.[34] Patients with triple-negative breast cancer had a shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival did not differ across breast cancer subtypes. Consideration of intrathecal administration of trastuzumab in patients with HER2-positive LC has also been reported in case reports.[35]

Metastatic Brain Tumors

Approximately 20% to 40% of cancer patients develop brain metastases, with a subsequent median survival generally less than 6 months. Common primary tumors with brain metastases include the following cancers:

  • Lung.
  • Breast.
  • Cancer of unknown primary.
  • Melanoma.
  • Colon.
  • Kidney.

The optimal therapy for patients with brain metastases continues to evolve.[32][36][37] Corticosteroids, anticonvulsants, radiation therapy, radiosurgery, and, possibly, surgical resection have roles in management. Because most cases of brain metastases involve multiple metastases, a mainstay of therapy has historically been WBRT, but stereotactic radiosurgery (SRS) has come into increasingly common use. The role of radiosurgery continues to be defined. Chemotherapy is usually not the primary therapy for most patients; however, it may have a role in the treatment of patients with brain metastases from chemosensitive tumors and can even be curative when combined with radiation for metastatic testicular germ cell tumors.[36][38] Intrathecal chemotherapy is also used for meningeal spread of metastatic tumors.

Treatment for patients with a single metastasis

About 10% to 15% of patients with cancer will have a single brain metastasis. Radiation therapy is the mainstay of palliation for these patients. The extent of extracranial disease can influence treatment of the brain lesions. In the presence of extensive active systemic disease, surgery provides little benefit for OS. In patients with stable minimal extracranial disease, combined modality treatment may be considered, using surgical resection followed by radiation therapy. However, the published literature does not provide clear guidance.

There have been three randomized trials of resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[39][40][41] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial, performed at a single center, all patients were selected and operated upon by one surgeon. The first two trials showed an improvement in survival in the surgery group, but the third showed a trend in favor of the WBRT-only group. The three trials were combined in a trial-level meta-analysis.[26] The combined analysis did not show a statistically significant difference in OS (HR = 0.72; 95% CI, 0.34–1.53; P = .4); nor was there a statistically significant difference in death from neurologic causes (RRdeath = 0.68; 95% CI, 0.43–1.09; P = .11). None of the trials assessed or reported quality of life. One of the trials reported that combined therapy increased the duration of functionally independent survival.[39][Level of evidence: 1iiD]

The need for WBRT after resection of solitary brain metastases has been tested.[42] Patients in the WBRT group were less likely to have tumor progression in the brain and were significantly less likely to die of neurological causes, but OS was the same, and there was no difference in duration of functional independence.[42] One additional randomized study of observation versus WBRT after either surgery or SRS for solitary brain metastases was closed because of slow accrual after 19 patients had been entered, so little can be deduced from the trial.[43] (Refer to the Treatment for patients with oligometastases (1–3 or 4 brain metastases) section of this summary for more information.)

Treatment for patients with oligometastases (1–3 or 4 brain metastases)

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[44] Patients with active systemic disease requiring therapy were excluded. The primary endpoint was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses). Mean OS in the combined-therapy and WBRT-alone groups was 5.7 months and 6.5 months, respectively (P = .14). In the subgroup with solitary metastases, OS was better in the combined-therapy group (6.5 months vs. 4.9 months; P =.039 in univariate analysis; P = .053 in a multivariable analysis adjusting for baseline prognostic factors); in patients with multiple metastases, survival was 5.8 months in the combined-therapy group versus 6.7 months in the WBRT-only group (P = .98). (The combined-treatment group had a survival advantage of 2½ months in patients with a single metastasis but not in patients with multiple lesions.) Local control was better in the full population with combined therapy.

At the 6-month follow-up, Karnofsky Performance status (considered a soft endpoint because of its imprecision and subjectivity) was better in the combined-therapy group, but there was no difference in mental status between the treatment groups. Acute and late toxicities were similar in both treatment arms. Quality of life was not assessed.[44][Levels of evidence: 1iiDii for the full study population and 1iiA for patients with solitary metastases]

The converse question has also been addressed—whether WBRT is necessary after focal treatment (i.e., resection or SRS) of oligometastases. Several randomized trials have been performed that were designed with varying primary endpoints.[45][46][47] However, the results can be summarized as follows:

  1. Studies consistently show that the addition of WBRT to focal therapy decreases the risk of progression and new metastases in the brain.
  2. The addition of WBRT does not improve OS.
  3. The decrease in risk of intracranial disease progression does not translate into improved functional or neurologic status, nor does it appear to decrease the risk of death from neurologic deterioration.
  4. About half or more of the patients who receive focal therapy alone ultimately require salvage therapy, such as WBRT or radiosurgery, compared with about a quarter of the patients who are given up-front WBRT.
  5. The impact of better local control associated with WBRT on quality of life has not been reported and remains an open question.

A phase III randomized trial compared adjuvant WBRT with observation after surgery or radiosurgery for a limited number of brain metastases in patients with stable solid tumors.[48] Health-related quality of life was improved in the observation-only arm compared with WBRT. Patients in the observation arm had better mean scores in physical, role, and cognitive functioning at 9 months. In an exploratory analysis, statistically significant worse scores for bladder control, communication deficit, drowsiness, hair loss, motor dysfunction, leg weakness, appetite loss, constipation, nausea/vomiting, pain, and social functioning were observed in patients who underwent WBRT compared with those who underwent observation only.[48][Level of evidence: 1iiC]

The study that had a primary endpoint of learning and neurocognition, using a standardized test for total recall, was stopped by the data and safety monitoring committee because of worse outcomes in the WBRT group.[46]

Given this body of information, focal therapy plus WBRT or focal therapy alone, with close follow-up with serial MRIs and initiation of salvage therapy when clinically indicated, appear to be reasonable treatment options. The pros and cons of each approach should be discussed with the patient.[46][Level of evidence: 1iiD]

Treatment for patients with multiple metastases

Patients with multiple brain metastases may be treated with WBRT. Surgery is indicated to obtain tissue from a metastasis with an unknown primary tumor or to decompress a symptomatic dominant lesion that is causing significant mass effect. SRS in combination with WBRT has been assessed. A meta-analysis of two trials with a total of 358 participants found no statistically significant difference in OS between the WBRT plus SRS and WBRT alone groups (HR, 0.82; 95% CI, 0.65–1.02). Patients in the WBRT plus SRS group had decreased local failure compared with patients who received WBRT alone (HR, 0.27; 95% CI, 0.14–0.52). Unchanged or improved Karnofsky Performance Scale at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in the WBRT group (P = .03).[49][Level of evidence: 1iiDiii]

References:

  1. Lallana EC, Abrey LE: Update on the therapeutic approaches to brain tumors. Expert Rev Anticancer Ther 3 (5): 655-70, 2003.

  2. Cloughesy T, Selch MT, Liau L: Brain. In: Haskell CM: Cancer Treatment. 5th ed. Philadelphia, Pa: WB Saunders Co, 2001, pp 1106-42.

  3. Nakamura M, Roser F, Michel J, et al.: The natural history of incidental meningiomas. Neurosurgery 53 (1): 62-70; discussion 70-1, 2003.

  4. Yano S, Kuratsu J; Kumamoto Brain Tumor Research Group: Indications for surgery in patients with asymptomatic meningiomas based on an extensive experience. J Neurosurg 105 (4): 538-43, 2006.

  5. Laws ER, Parney IF, Huang W, et al.: Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg 99 (3): 467-73, 2003.

  6. Chang SM, Parney IF, Huang W, et al.: Patterns of care for adults with newly diagnosed malignant glioma. JAMA 293 (5): 557-64, 2005.

  7. Meyer FB, Bates LM, Goerss SJ, et al.: Awake craniotomy for aggressive resection of primary gliomas located in eloquent brain. Mayo Clin Proc 76 (7): 677-87, 2001.

  8. Sanai N, Mirzadeh Z, Berger MS: Functional outcome after language mapping for glioma resection. N Engl J Med 358 (1): 18-27, 2008.

  9. Begg CB, Cramer LD, Hoskins WJ, et al.: Impact of hospital volume on operative mortality for major cancer surgery. JAMA 280 (20): 1747-51, 1998.

  10. Birkmeyer JD, Finlayson EV, Birkmeyer CM: Volume standards for high-risk surgical procedures: potential benefits of the Leapfrog initiative. Surgery 130 (3): 415-22, 2001.

  11. Barker FG 2nd, Curry WT Jr, Carter BS: Surgery for primary supratentorial brain tumors in the United States, 1988 to 2000: the effect of provider caseload and centralization of care. Neuro Oncol 7 (1): 49-63, 2005.

  12. Laperriere N, Zuraw L, Cairncross G, et al.: Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review. Radiother Oncol 64 (3): 259-73, 2002.

  13. Bleehen NM, Stenning SP: A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. Br J Cancer 64 (4): 769-74, 1991.

  14. Tsao MN, Mehta MP, Whelan TJ, et al.: The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Phys 63 (1): 47-55, 2005.

  15. Souhami L, Seiferheld W, Brachman D, et al.: Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 60 (3): 853-60, 2004.

  16. Karim AB, Afra D, Cornu P, et al.: Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 52 (2): 316-24, 2002.

  17. van den Bent MJ, Afra D, de Witte O, et al.: Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366 (9490): 985-90, 2005.

  18. Paulino AC, Mai WY, Chintagumpala M, et al.: Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys 71 (5): 1381-7, 2008.

  19. 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 303 (23): 1323-9, 1980.

  20. Stewart LA: Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359 (9311): 1011-8, 2002.

  21. Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.

  22. Stupp R, Hegi ME, Mason WP, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10 (5): 459-66, 2009.

  23. Valtonen S, Timonen U, Toivanen P, et al.: Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study. Neurosurgery 41 (1): 44-8; discussion 48-9, 1997.

  24. 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 5 (2): 79-88, 2003.

  25. Westphal M, Ram Z, Riddle V, et al.: Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien) 148 (3): 269-75; discussion 275, 2006.

  26. Hart MG, Grant R, Garside R, et al.: Chemotherapeutic wafers for high grade glioma. Cochrane Database Syst Rev (3): CD007294, 2008.

  27. Fine HA: Promising new therapies for malignant gliomas. Cancer J 13 (6): 349-54, 2007 Nov-Dec.

  28. Fecci PE, Mitchell DA, Archer GE, et al.: The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors. J Neurooncol 64 (1-2): 161-76, 2003 Aug-Sep.

  29. Newton HB: Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways. Expert Rev Anticancer Ther 3 (5): 595-614, 2003.

  30. Kew Y, Levin VA: Advances in gene therapy and immunotherapy for brain tumors. Curr Opin Neurol 16 (6): 665-70, 2003.

  31. Chiocca EA, Aghi M, Fulci G: Viral therapy for glioblastoma. Cancer J 9 (3): 167-79, 2003 May-Jun.

  32. Mehta M, Vogelbaum MA, Chang S, et al.: Neoplasms of the central nervous system. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1700-49.

  33. Lee SJ, Lee JI, Nam DH, et al.: Leptomeningeal carcinomatosis in non-small-cell lung cancer patients: impact on survival and correlated prognostic factors. J Thorac Oncol 8 (2): 185-91, 2013.

  34. Torrejón D, Oliveira M, Cortes J, et al.: Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis. Breast 22 (1): 19-23, 2013.

  35. Bartsch R, Berghoff AS, Preusser M: Optimal management of brain metastases from breast cancer. Issues and considerations. CNS Drugs 27 (2): 121-34, 2013.

  36. Patchell RA: The management of brain metastases. Cancer Treat Rev 29 (6): 533-40, 2003.

  37. Soffietti R, Cornu P, Delattre JY, et al.: EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur J Neurol 13 (7): 674-81, 2006.

  38. Ogawa K, Yoshii Y, Nishimaki T, et al.: Treatment and prognosis of brain metastases from breast cancer. J Neurooncol 86 (2): 231-8, 2008.

  39. Patchell RA, Tibbs PA, Walsh JW, et al.: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322 (8): 494-500, 1990.

  40. Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al.: Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 33 (6): 583-90, 1993.

  41. Mintz AH, Kestle J, Rathbone MP, et al.: A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 78 (7): 1470-6, 1996.

  42. Patchell RA, Tibbs PA, Regine WF, et al.: Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280 (17): 1485-9, 1998.

  43. Roos DE, Wirth A, Burmeister BH, et al.: Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05). Radiother Oncol 80 (3): 318-22, 2006.

  44. Andrews DW, Scott CB, Sperduto PW, et al.: Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363 (9422): 1665-72, 2004.

  45. Aoyama H, Shirato H, Tago M, et al.: Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295 (21): 2483-91, 2006.

  46. Chang EL, Wefel JS, Hess KR, et al.: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10 (11): 1037-44, 2009.

  47. Kocher M, Soffietti R, Abacioglu U, et al.: Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29 (2): 134-41, 2011.

  48. Soffietti R, Kocher M, Abacioglu UM, et al.: A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 31 (1): 65-72, 2013.

  49. Patil CG, Pricola K, Sarmiento JM, et al.: Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev 9: CD006121, 2012.

Management of Specific Tumor Types and Locations

Brain Stem Gliomas

Standard treatment options:

  • Radiation therapy.

Patients with brain stem gliomas have relatively poor prognoses that correlate with histology (when biopsies are performed), location, and extent of tumor. The overall median survival time of patients in studies has been 44 to 74 weeks.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Pineal Astrocytic Tumors

Standard treatment options:

  1. Surgery plus radiation therapy for patients with pilocytic or diffuse astrocytoma.
  2. Surgery plus radiation therapy and chemotherapy for patients with higher grade tumors.

Depending on the degree of anaplasia, patients with pineal astrocytomas vary in prognoses. Higher grades have worse prognoses.

Pilocytic Astrocytomas

Standard treatment options:

  1. Surgery alone if the tumor is totally resectable.
  2. Surgery followed by radiation therapy to known or suspected residual tumor.

This astrocytic tumor is classified as a World Health Organization (WHO) grade I tumor and is often curable.

Diffuse Astrocytomas (WHO grade II)

Standard treatment options:

  • Surgery plus radiation therapy; however, some controversy exists. Some physicians treat these patients with surgery alone if the patient is younger than 35 years and if the tumor does not contrast-enhance on a computed tomographic scan.[1]

This WHO grade II astrocytic tumor is less often curable than is a pilocytic astrocytoma.

Anaplastic Astrocytomas (WHO grade III)

Standard treatment options:

  1. Surgery plus radiation therapy.
  2. Surgery plus radiation therapy and chemotherapy.

Patients with anaplastic astrocytomas (WHO grade III) have a low cure rate with standard local treatment. Because anaplastic astrocytomas represent less than 10% of all central nervous system gliomas, phase III randomized trials restricted to patients with them are not practical. However, because these tumors are often aggressive, they are frequently managed the same way as glioblastomas, with surgery and radiation, and often with chemotherapy, even though it is not known whether the improved survival with chemotherapy in glioblastoma can be extrapolated to anaplastic astrocytomas.

Postoperative radiation alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either procarbazine + lomustine + vincristine (PCV) or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect time to treatment failure (TTF) or overall survival (OS).[2][Levels of evidence: 1iiA and 1iiD] Neither TTF nor OS differed across the treatment arms.

Patients with anaplastic astrocytomas are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. Information about ongoing clinical trials is available from the NCI Web site.

Glioblastomas

Standard treatment options for patients with newly diagnosed disease:

  1. Surgery plus radiation therapy.
  2. Surgery plus radiation therapy and chemotherapy.
  3. Carmustine-impregnated polymer implanted during initial surgery.
  4. Radiation therapy and concurrent chemotherapy.

The standard-of-care treatment for patients with newly diagnosed glioblastoma is surgery followed by concurrent radiation therapy and daily temozolomide, and then followed by six cycles of temozolomide. This standard therapy is based on a large, multicenter, randomized trial (NCT00006353) conducted by the European Organization for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada (NCIC), which reported a survival benefit with concurrent radiation therapy and temozolomide compared with radiation therapy alone.[3][4][Level of evidence: 1iiA] In that study, 573 patients with glioblastoma were randomly assigned to receive standard radiation to the tumor volume with a 2- to 3-cm margin (60 Gy, 2 Gy per fraction, over 6 weeks) alone or with temozolomide (75 mg/m2 orally per day during radiation therapy for up to 49 days, followed by a 4-week break and then up to six cycles of five daily doses every 28 days at a dose of 150 mg/m2, increasing to 200 mg/m2 after the first cycle). Patients in the combined therapy group were given prophylactic therapy for pneumocystis carinii during the period of concomitant radiation therapy and temozolomide. OS was statistically significantly better in the combined radiation therapy–temozolomide group (hazard ratio [HR]death, 0.6; 95% confidence interval [CI], 0.5–0.7; OS at 3 years was 16.0% vs. 4.4%).

O6-methylguanine–DNA methyltransferase (MGMT) promoter DNA methylation

A companion molecular, correlation subset study to the EORTC-NCIC trial provided strong evidence that epigenetic silencing of the MGMT DNA-repair gene by promoter DNA methylation was associated with increased OS in patients with newly diagnosed glioblastoma.[5] MGMT promoter methylation was an independent favorable prognostic factor (P < .001 by the log-rank test; HR, 0.45; 95% CI, 0.32–0.61). The median OS for MGMT-methylated patients was 18.2 months (95% CI, 15.5–22.0), compared with 12.2 months (95% CI, 11.4–13.5) for MGMT-unmethylated patients.

Dose-dense temozolomide

MGMT DNA-repair activity has been proposed as a major mechanism of resistance to alkylating agents. Intracellular depletion of MGMT has been hypothesized to enhance treatment response, and protracted temozolomide schedules have been shown to deplete intracellular MGMT in peripheral blood mononuclear cells. To test whether protracted temozolomide enhances treatment response in patients with newly diagnosed glioblastoma, a multicenter, randomized, phase III trial conducted by the Radiation Therapy Oncology Group (RTOG), EORTC, and the North Central Cancer Therapy Group, RTOG 0525 (NCT00304031), compared standard adjuvant temozolomide treatment (days 1–5 of a 28-day cycle) with a dose-dense schedule (days 1–21 of a 28-day cycle). All patients were treated with surgery followed by radiation therapy and concurrent daily temozolomide. Patients were then randomly assigned to receive either standard adjuvant temozolomide or dose-dense temozolomide.[6][Level of evidence: 1iiA]

Among 833 randomly assigned patients, no statistically significant difference between standard and dose-dense temozolomide was observed for median OS (16.6 months for standard temozolomide vs. 14.9 months for dose-dense temozolomide; HR, 1.03; P = .63) or median progression-free survival (PFS) (5.5 vs. 6.7 months; HR, 0.87; P = .06). MGMT status was determined in 86% of randomly assigned patients, and no difference in efficacy was observed in either the MGMT-methylated or MGMT-unmethylated subsets. However, this study confirmed the strong prognostic effect of MGMT methylation because the median OS was 21.2 months (95% CI, 17.9–24.8) for methylated patients versus 14 months (95% CI, 12.9–14.7) (HR, 1.74; P < .001) for unmethylated patients.

In summary, there was no survival advantage for the use of dose-dense temozolomide versus standard-dose temozolomide in newly diagnosed glioblastoma patients, regardless of MGMT status. The efficacy of dose-dense temozolomide for patients who have recurrent glioblastoma, however, is yet to be determined.

Bevacizumab in newly diagnosed glioblastoma

In 2013, final data from two multicenter, phase III, randomized, double-blind, placebo-controlled trials of bevacizumab in patients who have newly diagnosed glioblastoma were reported: RTOG 0825 (NCT00884741) and the Roche-sponsored AVAglio (NCT00943826).[7][8][Level of evidence: 1iA] Patients in both studies were randomly assigned to receive standard therapy (chemoradiation with temozolomide) or standard therapy plus bevacizumab. OS and PFS were coprimary endpoints in both trials, and these outcomes were similar. Bevacizumab did not improve OS in either study (median OS was 16–17 months for each arm in both studies); however, it increased median PFS to a similar degree (AVAglio study: 10.6 vs. 6.2 months; HR, 0.64; P < .0001; RTOG 0825 study: 10.7 vs. 7.3 months; HR, 0.79; P = .007). The PFS result in the AVAglio study was statistically significant and associated with clinical benefit because bevacizumab-treated patients remained functionally independent for longer (9.0 months vs. 6.0 months) and went longer before their Karnofsky Performance scale deteriorated (HR, 0.65; P < .0001). Furthermore, bevacizumab-treated patients went longer before corticosteroids were initiated (12.3 vs. 3.7 months; HR, 0.71; P = .002), and a larger proportion of patients was able to discontinue corticosteroids if they were already taking them (66% vs. 47%). However, the PFS result in the RTOG 0825 trial did not meet the prespecified significance level (P = .004). Of note, there was significant crossover in both trials (approximately 40% of RTOG 0825 patients and approximately 30% of AVAglio patients received bevacizumab at the first sign of disease progression).

The two trials had contradictory results in health-related quality of life (HRQoL) and neurocognitive outcomes studies. In the mandatory HRQoL studies in the AVAglio trial, bevacizumab-treated patients experienced improved HRQoL, but bevacizumab-treated patients in the elective RTOG 0825 studies showed more decline in patient-reported HRQoL and neurocognitive function. The reasons for these discrepancies are unclear.

On the basis of these results, there is no definite evidence that the addition of bevacizumab to standard therapy is beneficial for all newly diagnosed glioblastoma patients. It is yet to be determined whether certain subgroups may benefit from the addition of bevacizumab.

For patients with glioblastoma (WHO grade IV), the cure rate is very low with standard local treatment. These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. Information about ongoing clinical trials is available from the NCI Web site.

Oligodendroglial Tumors

Oligodendrogliomas

Standard treatment options:

  • Surgery plus radiation therapy; however, some controversy exists concerning the timing of radiation therapy. A study (EORTC-22845) of 300 patients who had surgery and were randomly assigned to either radiation therapy or watch and wait did not show a difference in OS in the two groups.[9][Level of evidence: 1iiA]

Patients who have oligodendrogliomas (WHO grade II) generally have better prognoses than do patients who have diffuse astrocytomas; however, most of the oligodendrogliomas eventually progress.

Anaplastic oligodendrogliomas

Standard treatment options:

  1. Surgery plus radiation therapy.
  2. Surgery plus radiation therapy plus chemotherapy.[10]
  3. Patients with an allelic loss at 1p and 19q have a higher than average response rate to PCV chemotherapy.

Mature results from the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group Study 26951 (NCT00002840), a phase III, randomized study with 11.7 years of follow up demonstrated increased OS and progression-free survival in patients with anaplastic oligodendroglial tumors with six cycles of adjuvant PCV chemotherapy after radiation therapy compared with radiation therapy alone.[11] The OS was significantly longer in the radiation therapy and PCV arm (42.3 months vs. 30.6 months; HR, 0.75; 95% CI, 0.60–0.95). 1p/19q-codeleted tumors derived more benefit from adjuvant PCV chemotherapy compared with non-1p/19q-deleted tumors.[11][Level of evidence: 1iiA]

In contrast, the Radiation Therapy Oncology Group (RTOG) trial (RTOG-9402 [NCT00002569]) demonstrated no differences in median survival by treatment arm between an 8-week, intensive PCV chemotherapy regimen followed by immediate involved-field-plus-radiation therapy and radiation therapy alone.[12] However, in an unplanned subgroup analysis, patients with 1p/19q codeleted anaplastic oligodendroglioma and mixed anaplastic astrocytoma demonstrated a median survival of 14.7 years versus 7.3 years (HR, 0.59; 95% CI, 0.37–0.95; P = .03). For patients with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 vs. 2.7 years; HR, 0.85; 95% CI, 0.58–1.23; P = .39).[12][Level of evidence: 1iiA]

On the basis of these data, CODEL, a study that randomly assigned patients to radiation therapy alone (control arm), radiation therapy with temozolomide, and temozolomide alone (exploratory arm), was halted because radiation therapy alone was no longer considered adequate treatment in patients with anaplastic oligodendroglioma with 1p/19q codeletion.[13] A comparison between temozolomide and PCV chemotherapy in anaplastic oligodendroglioma has not been done, although in the setting of grade 3 anaplastic gliomas, no survival difference was seen between PCV chemotherapy and temozolomide.[2][14]

Patients with anaplastic oligodendrogliomas (WHO grade III) have a low cure rate with standard local treatment, but their prognoses are generally better than are the prognoses of patients with anaplastic astrocytomas. Since anaplastic oligodendrogliomas are uncommon, phase III randomized trials restricted to patients with them are not practical. Patients with these tumors are generally managed with the following:

  • Postoperative radiation therapy (PORT) alone, with chemotherapy at progression.
  • Postoperative chemotherapy with radiation at progression.
  • PORT plus chemotherapy, even though the combination of radiation plus chemotherapy is not known to be superior in outcome to sequential modality therapy.

PORT alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either PCV or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect TTF or OS.[2][Levels of evidence: 1iiA and 1iiD]. Neither TTF nor OS differed across the treatment arms.

These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment. Information about ongoing clinical trials is available from the NCI Web site.

Mixed Gliomas

Standard treatment options:

  1. Surgery plus radiation therapy.
  2. Surgery plus radiation therapy plus chemotherapy.

Patients with mixed glial tumors, which include oligoastrocytoma (WHO grade II) and anaplastic oligoastrocytoma (WHO grade III), have prognoses similar to that for astrocytic tumors of corresponding grades and are often treated as such.

Ependymal Tumors

Grade I and II ependymal tumors

Standard treatment options:

  1. Surgery alone if the tumor is totally resectable.
  2. Surgery followed by radiation therapy to known or suspected residual tumor.

Ependymomas (WHO grade II) and ependymal tumors (WHO grade I), i.e., subependymoma and myxopapillary ependymomas, are often curable.

Anaplastic ependymomas

Standard treatment options:

  • Surgery plus radiation therapy.[15]

Patients with anaplastic ependymomas (WHO grade III) have variable prognoses that depend on the location and extent of disease. Frequently, but not invariably, patients with anaplastic ependymomas have worse prognoses than do those patients with lower-grade ependymal tumors.

Embryonal Cell Tumors: Medulloblastomas

Standard treatment options:

  • Surgery plus craniospinal radiation therapy for good-risk patients.[16]

Treatment options under clinical evaluation:

  • Surgery plus craniospinal radiation therapy and various chemotherapy regimens are being evaluated for poor-risk patients.[16]

Medulloblastoma occurs primarily in children, but it also occurs with some frequency in adults.[17] Other embryonal tumors are pediatric conditions. (Refer to the PDQ summary on Childhood Central Nervous System Embryonal Tumors Treatment for more information.)

Pineal Parenchymal Tumors

Standard treatment options:

  1. Surgery plus radiation therapy for pineocytoma.
  2. Surgery plus radiation therapy and chemotherapy for pineoblastoma.

Pineocytoma (WHO grade II), pineoblastoma (WHO grade IV), and pineal parenchymal tumors of intermediate differentiation are diverse tumors that require special consideration. Pineocytomas are slow-growing tumors, and patients with them carry variable prognoses for cure. Pineoblastomas are more rapidly growing tumors, and patients with them have worse prognoses. Pineal parenchymal tumors of intermediate differentiation have unpredictable growth and clinical behavior.

Meningeal Tumors

Grade I meningiomas

Standard treatment options:

  1. Active surveillance with deferred treatment, especially for incidentally discovered asymptomatic tumors.[18][19].
  2. Surgery.
  3. Stereotactic radiosurgery for tumors less than 3 cm.
  4. Surgery plus radiation therapy is used in selected cases, such as for patients with known or suspected residual disease or with recurrence after previous surgery.
  5. Fractionated radiation therapy for patients with unresectable tumors.[20]

WHO grade I meningiomas are usually curable when the mengiomas are resectable. With the increasing use of sensitive neuroimaging tools, there has been greater detection of asymptomatic low-grade meningiomas. The majority appear to show minimal growth and can often be safely observed while therapy is deferred until growth or the development of symptoms.[18][19]

Grade II and III meningiomas and hemangiopericytomas

Standard treatment options:

  • Surgery plus radiation therapy.

The prognoses for patients with meningiomas (WHO grade II) (i.e., atypical, clear cell, and chordoid), meningiomas (WHO grade III) (i.e., anaplastic/malignant, rhabdoid, and papillary), and hemangiopericytomas are worse than are those for patients with low-grade meningiomas because complete resections are less commonly feasible, and the proliferative capacity is greater.

Germ Cell Tumors

The prognoses and treatment of patients with germ cell tumors—which include germinoma, embryonal carcinoma, choriocarcinoma, and teratoma—depend on tumor histology, tumor location, presence and amount of biological markers, and surgical resectability.

Tumors of the Sellar Region: Craniopharyngiomas

Standard treatment options:

  1. Surgery alone if the tumor is totally resectable.
  2. Debulking surgery plus radiation therapy if the tumor is unresectable.

Craniopharyngiomas (WHO grade I) are often curable.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kaye AH, Walker DG: Low grade astrocytomas: controversies in management. J Clin Neurosci 7 (6): 475-83, 2000.

  2. Wick W, Hartmann C, Engel C, et al.: NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27 (35): 5874-80, 2009.

  3. Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.

  4. Stupp R, Hegi ME, Mason WP, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10 (5): 459-66, 2009.

  5. Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005.

  6. Gilbert MR, Wang M, Aldape KD, et al.: Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol 31 (32): 4085-91, 2013.

  7. Gilbert MR, Dignam JJ, Armstrong TS, et al.: A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370 (8): 699-708, 2014.

  8. Chinot OL, Wick W, Mason W, et al.: Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370 (8): 709-22, 2014.

  9. van den Bent MJ, Afra D, de Witte O, et al.: Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366 (9490): 985-90, 2005.

  10. van den Bent MJ, Chinot O, Boogerd W, et al.: Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. Ann Oncol 14 (4): 599-602, 2003.

  11. van den Bent MJ, Brandes AA, Taphoorn MJ, et al.: Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31 (3): 344-50, 2013.

  12. Cairncross G, Wang M, Shaw E, et al.: Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31 (3): 337-43, 2013.

  13. Gilbert MR: Minding the Ps and Qs: perseverance and quality studies lead to major advances in patients with anaplastic oligodendroglioma. J Clin Oncol 31 (3): 299-300, 2013.

  14. Brada M, Stenning S, Gabe R, et al.: Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol 28 (30): 4601-8, 2010.

  15. Oya N, Shibamoto Y, Nagata Y, et al.: Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure. J Neurooncol 56 (1): 87-94, 2002.

  16. Brandes AA, Franceschi E, Tosoni A, et al.: Long-term results of a prospective study on the treatment of medulloblastoma in adults. Cancer 110 (9): 2035-41, 2007.

  17. Brandes AA, Ermani M, Amista P, et al.: The treatment of adults with medulloblastoma: a prospective study. Int J Radiat Oncol Biol Phys 57 (3): 755-61, 2003.

  18. Nakamura M, Roser F, Michel J, et al.: The natural history of incidental meningiomas. Neurosurgery 53 (1): 62-70; discussion 70-1, 2003.

  19. Yano S, Kuratsu J; Kumamoto Brain Tumor Research Group: Indications for surgery in patients with asymptomatic meningiomas based on an extensive experience. J Neurosurg 105 (4): 538-43, 2006.

  20. Debus J, Wuendrich M, Pirzkall A, et al.: High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas: long-term results. J Clin Oncol 19 (15): 3547-53, 2001.

Recurrent Adult Brain Tumors

Surgery

Re-resection of recurrent brain tumors is used in some patients. However, the majority of patients do not qualify because of a deteriorating condition or technically inoperable tumors. The evidence is limited to noncontrolled studies and case series on patients who are healthy enough and have small enough tumors to technically debulk. The impact of reoperation versus patient selection on survival is not known.

Localized Chemotherapy

Carmustine wafers have been investigated in the setting of recurrent malignant gliomas, but the impact on survival is less clear than at the time of initial diagnosis and resection. In a multicenter randomized, placebo-controlled trial, 222 patients with recurrent malignant primary brain tumors requiring reoperation were randomly assigned to receive implanted carmustine wafers or placebo biodegradable wafers.[1] Approximately half of the patients had received prior systemic chemotherapy. The two treatment groups were well balanced at baseline. Median survival was 31 versus 23 weeks in the two groups. The statistical significance between the two overall survival (OS) curves depended upon the method of analysis. The hazard ratio (HR) for risk of dying in the direct intention-to-treat comparison between the two groups was 0.83 (95% confidence interval [CI], 0.63–1.10; P = .19). The baseline characteristics were similar in the two groups, but the investigators did an additional analysis, adjusting for prognostic factors, because they felt that even small differences in baseline characteristics could have a powerful influence on outcomes. In the adjusted proportional hazards model, the HR for risk of death was 0.67 (95% CI, 0.51–0.90, P = .006). The investigators put their emphasis on this latter analysis and reported this as a positive trial.[1][Level of evidence: 1iA] However, a Cochrane Collaboration systematic review of chemotherapeutic wafers for high-grade glioma focused on the unadjusted analysis and reported the same trial as negative.[2]

Systemic Chemotherapy

Bevacizumab

In 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval of bevacizumab monotherapy for patients with progressive glioblastoma. The indication was granted under the FDA’s accelerated approval program that permits the use of certain surrogate endpoints or an effect on a clinical endpoint other than survival or irreversible morbidity as bases for approvals of products intended for serious or life-threatening illnesses or conditions. The approval was based on the demonstration of improved objective response rates observed in two historically controlled, single-arm, or noncomparative phase II trials.[3][4][Level of evidence: 3iiiDiv]

The FDA independently reviewed an open-label, multicenter, noncomparative phase II study that randomly assigned 167 recurrent glioblastoma multiforme (GBM) patients to receive bevacizumab alone or bevacizumab in combination with irinotecan,[3] although only efficacy data from the bevacizumab monotherapy arm (n = 85) were used to support drug approval. According to the FDA analysis of this study, tumor responses were observed in 26% of patients treated with bevacizumab alone, and the median duration of response in these patients was 4.2 months. On the basis of this externally controlled trial, the incidence of adverse events associated with bevacizumab did not appear to be significantly increased in GBM patients. The FDA independently assessed another single-arm, single-institution trial in which 56 recurrent glioblastoma patients were treated with bevacizumab alone.[4] Responses were observed in 20% of patients, and the median duration of response was 3.9 months.

Currently, however, no data are available from prospective, randomized controlled trials demonstrating improvement in health outcomes, such as disease-related symptoms or increased survival with the use of bevacizumab to treat glioblastoma. On the basis of these data and FDA approval, bevacizumab monotherapy has become standard therapy for recurrent glioblastoma.

Systemic Chemotherapy

Systemic therapy (e.g., temozolomide, lomustine, or the combination of procarbazine, a nitrosourea, and vincristine in patients who have not previously received the drugs) has been used at the time of recurrence of primary malignant brain tumors. However, it has not been tested in controlled studies. Patient-selection factors likely play a strong role in determining outcomes, so the impact of therapy on survival is not clear.

Radiation Therapy

Because there are no randomized trials, the role of repeat radiation after disease progression or the development of radiation-induced cancers is also ill defined. Interpretation is difficult because the literature is limited to small retrospective case series.[5] The decision must be made carefully because of the risk of neurocognitive deficits and radiation necrosis.

Patients who have recurrent brain tumors are rarely curable and should be considered candidates for clinical trials when they have exhausted standard therapy. Information about ongoing clinical trials is available from the NCI Web site.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult brain tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. 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 345 (8956): 1008-12, 1995.

  2. Hart MG, Grant R, Garside R, et al.: Chemotherapeutic wafers for high grade glioma. Cochrane Database Syst Rev (3): CD007294, 2008.

  3. Friedman HS, Prados MD, Wen PY, et al.: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27 (28): 4733-40, 2009.

  4. Kreisl TN, Kim L, Moore K, et al.: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27 (5): 740-5, 2009.

  5. Paulino AC, Mai WY, Chintagumpala M, et al.: Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys 71 (5): 1381-7, 2008.


This information is provided by the National Cancer Institute.

This information was last updated on February 28, 2014.

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