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Neuroblastoma Treatment (PDQ®)

Patient Version
Last Modified: 08/28/2014

General Information About Neuroblastoma



Neuroblastoma is a disease in which malignant (cancer) cells form in nerve tissue of the adrenal gland, neck, chest, or spinal cord.

Neuroblastoma often begins in the nerve tissue of the adrenal glands. There are two adrenal glands, one on top of each kidney in the back of the upper abdomen. The adrenal glands make important hormones that help control heart rate, blood pressure, blood sugar, and the way the body reacts to stress. Neuroblastoma may also begin in the abdomen, in the chest, in nerve tissue near the spine in the neck, or in the spinal cord.

Enlarge
Drawing shows parts of the body where neuroblastoma may be found, including the paraspinal nerve tissue and the adrenal glands. Also shown are the spine and right and left kidney.
Neuroblastoma may be found in the adrenal glands and paraspinal nerve tissue from the neck to the pelvis.


Neuroblastoma most often begins during early childhood, usually in children younger than 5 years of age. It is found when the tumor begins to grow and cause signs or symptoms. Sometimes it forms before birth and is found during a fetal ultrasound.

By the time neuroblastoma is diagnosed, the cancer has usually metastasized (spread). Neuroblastoma spreads most often to the lymph nodes, bones, bone marrow, liver, and in infants, skin.

See the PDQ summary on Neuroblastoma Screening for more information.

Neuroblastoma is sometimes caused by a gene mutation (change) passed from the parent to the child.

Neuroblastoma is sometimes inherited (passed from the parent to the child). Neuroblastoma that is inherited usually occurs at a younger age than neuroblastoma that is not inherited. In inherited neuroblastoma, more than one tumor may form in the adrenal medulla.

Signs and symptoms of neuroblastoma include bone pain and a lump in the abdomen, neck, or chest.

The most common signs and symptoms of neuroblastoma are caused by the tumor pressing on nearby tissues as it grows or by cancer spreading to the bone. These and other signs and symptoms may be caused by neuroblastoma or by other conditions.

Check with your child’s doctor if your child has any of the following:

  • Lump in the abdomen, neck, or chest.
  • Bulging eyes.
  • Dark circles around the eyes ("black eyes").
  • Bone pain.
  • Swollen stomach and trouble breathing (in infants).
  • Painless, bluish lumps under the skin (in infants).
  • Weakness or paralysis (loss of ability to move a body part).

Less common signs and symptoms of neuroblastoma include the following:

  • Fever.
  • Shortness of breath.
  • Feeling tired.
  • Easy bruising or bleeding.
  • Petechiae (flat, pinpoint spots under the skin caused by bleeding).
  • High blood pressure.
  • Severe watery diarrhea.
  • Jerky muscle movements.
  • Uncontrolled eye movement.

Tests that examine many different body tissues and fluids are used to detect (find) and diagnose neuroblastoma.

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.

  • Urine catecholamine studies: A procedure in which a urine sample is checked to measure the amount of certain substances, vanillylmandelic acid (VMA) and homovanillic acid (HVA), that are made when catecholamines break down and are released into the urine. A higher than normal amount of VMA or HVA can be a sign of neuroblastoma.

  • Blood chemistry studies : A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. A higher than normal amount of the hormones dopamine and norepinephrine may be a sign of neuroblastoma.

  • mIBG (metaiodobenzylguanidine) scan : A procedure used to find neuroendocrine tumors, such as neuroblastoma and pheochromocytoma. A very small amount of a substance called radioactive mIBG is injected into a vein and travels through the bloodstream. Neuroendocrine tumor cells take up the radioactive mIBG and are detected by a scanner. Scans may be taken over 1-3 days. An iodine solution may be given before or during the test to keep the thyroid gland from absorbing too much of the mIBG. This test is also used to find out how well the tumor is responding to treatment. mIBG is used in high doses to treat neuroblastoma.

  • Bone marrow aspiration and biopsy : The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.

  • X-ray : An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

  • 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 areas inside the body. 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).

  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.

A biopsy is done to diagnose neuroblastoma.

Cells and tissues are removed during a biopsy so they can be viewed under a microscope by a pathologist to check for signs of cancer. The way the biopsy is done depends on where the tumor is in the body. Sometimes the whole tumor is removed at the same time the biopsy is done.

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

  • 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.

  • 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.

  • 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.

  • MYC-N amplification study: A laboratory study in which tumor or bone marrow cells are checked for the level of MYC-N. MYC-N is important for cell growth. A higher level of MYC-N (more than 10 copies of the gene) is called MYC-N amplification. Neuroblastoma with MYC-N amplification is more likely to spread in the body and less likely to respond to treatment.

Children who are 6 months old or younger may not need a biopsy or surgery to remove the tumor because the tumor may disappear without treatment.

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

The prognosis (chance of recovery) and treatment options depend on the following:

  • Age of the child at diagnosis.
  • Stage of the cancer.
  • Tumor histology (the shape, function, and structure of the tumor cells).
  • Whether there is cancer in the lymph nodes on the same side of the body as the cancer or whether there is cancer in the lymph nodes on the opposite side of the body.
  • How the tumor responds to treatment.
  • Whether there are certain changes in the chromosomes.
  • How much time passed between diagnosis and when the cancer recurred (for recurrent cancer).

Prognosis and treatment options for neuroblastoma are also affected by tumor biology, which includes:

  • The patterns of the tumor cells.
  • How different the tumor cells are from normal cells.
  • How fast the tumor cells are growing.
  • Whether the tumor shows MYC-N amplification.

The tumor biology is said to be favorable or unfavorable, depending on these factors. A favorable tumor biology means there is a better chance of recovery.

In some children who are 6 months old and younger, neuroblastoma may disappear without treatment. The child is closely watched for signs or symptoms of neuroblastoma. If signs or symptoms occur, treatment may be needed.

Stages of Neuroblastoma



After neuroblastoma has been diagnosed, tests are done to find out if cancer has spread from where it started to other parts of the body.

The process used to find out the extent or spread of cancer is called staging. The information gathered from the staging process helps determine the stage of the disease. For neuroblastoma, stage is one of the factors used to plan treatment. The results of tests and procedures used to diagnose neuroblastoma may also be used for staging. See the General Information section for a description of these tests and procedures.

The following tests and procedures also may be used to determine the stage:

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if neuroblastoma spreads to the liver, the cancer cells in the liver are actually neuroblastoma cells. The disease is metastatic neuroblastoma, not liver cancer.

The following stages are used for neuroblastoma:

Stage 1

In stage 1, the tumor is in only one area and all of the tumor that can be seen is completely removed during surgery.

Stage 2

Stage 2 is divided into stages 2A and 2B.

Stage 3

In stage 3, one of the following is true:

  • the tumor cannot be completely removed during surgery and has spread from one side of the body to the other side and may also have spread to nearby lymph nodes; or
  • the tumor is in only one area, on one side of the body, but has spread to lymph nodes on the other side of the body; or
  • the tumor is in the middle of the body and has spread to tissues or lymph nodes on both sides of the body, and the tumor cannot be removed by surgery.

Stage 4

Stage 4 is divided into stages 4 and 4S.

Treatment of neuroblastoma is based on risk groups.

For many types of cancer, stages are used to plan treatment. For neuroblastoma, treatment depends on risk groups. The stage of neuroblastoma is one factor used to determine risk group. Other factors are the age of the child, tumor histology, and tumor biology.

There are three risk groups: low risk, intermediate risk, and high risk.

  • Low-risk and intermediate-risk neuroblastoma have a good chance of being cured.
  • High-risk neuroblastoma may be hard to cure.

Recurrent Neuroblastoma

Recurrent neuroblastoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the same place or in other parts of the body.

Treatment Option Overview



There are different types of treatment for patients with neuroblastoma.

Different types of treatment are available for patients with neuroblastoma. 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.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with neuroblastoma should have their treatment planned by a team of doctors with expertise in treating childhood cancer, especially neuroblastoma.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health care providers who are experts in treating children with neuroblastoma and who specialize in certain areas of medicine. These may include the following specialists:

Children who are treated for neuroblastoma may have an increased risk of second cancers.

Some cancer treatments cause side effects that continue or appear years after cancer treatment has ended. These are called late effects. Late effects of cancer treatment may include:

  • Physical problems.
  • Changes in mood, feelings, thinking, learning, or memory.
  • Second cancers (new types of cancer).

Some late effects may be treated or controlled. It is important that parents of children who are treated for neuroblastoma talk with their doctors about the possible late effects caused by some treatments. See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.

Five types of standard treatment are used:

Observation

Observation is closely monitoring a patient's condition without giving any treatment until signs or symptoms appear or change.

Surgery

Surgery is used to treat neuroblastoma unless it has spread to other parts of the body. Depending on where the tumor is, as much of the tumor as is safely possible will be removed. If the tumor cannot be removed, a biopsy may be done instead.

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 and stage of the cancer being treated. External radiation therapy is used to treat neuroblastoma.

High-risk neuroblastoma that comes back after initial treatment is sometimes treated with mIBG (radioactive iodine therapy). Radioactive iodine is given through an intravenous (IV) line and enters the bloodstream which carries radiation directly to tumor cells. Radioactive iodine collects in neuroblastoma cells and kills them with the radiation that is given off.

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). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

The use of two or more anticancer drugs is called combination chemotherapy.

See Drugs Approved for Neuroblastoma for more information.

High-dose chemotherapy and radiation therapy with stem cell rescue

High-dose chemotherapy and radiation therapy with stem cell rescue is a way of giving high doses of chemotherapy and radiation therapy and replacing blood -forming cells destroyed by cancer treatment for high-risk neuroblastoma. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient and are frozen and stored. After chemotherapy and radiation therapy are completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

Maintenance therapy is given after high-dose chemotherapy and radiation therapy with stem cell rescue to kill any cancer cells that may regrow and cause the disease to come back. Maintenance therapy is given for 6 months and includes the following treatments:

  • Isotretinoin: A vitamin -like drug that slows the cancer's ability to make more cancer cells and changes how these cells look and act. This drug is taken by mouth.
  • Anti-GD2 antibody ch14.18: A type of monoclonal antibody therapy that uses an antibody (ch14.18) made in the laboratory from a single type of immune system cell. ch14.18 identifies and attaches to a substance, called GD2, on the surface of neuroblastoma cells. Once the ch14.18 attaches to the GD2, a signal is sent to the immune system that a foreign substance has been found and needs to be killed. Then the body's immune system kills the neuroblastoma cell. This drug is given by infusion.
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF): A cytokine that helps make more immune system cells, especially granulocytes and macrophages (white blood cells), which can attack and kill cancer cells.
  • Interleukin-2 (IL-2): A type of biologic therapy that boosts the growth and activity of many immune cells, especially lymphocytes (a type of white blood cell). Lymphocytes can attack and kill cancer cells.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

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. Tyrosine kinase inhibitor (TKI) therapy is one type of targeted therapy being studied in the treatment of neuroblastoma.

TKI therapy blocks signals needed for tumors to grow. TKIs block the enzyme, tyrosine kinase, that causes stem cells to become more white blood cells (granulocytes or blasts) than the body needs. Crizotinib is one of the TKIs being studied to treat neuroblastoma that has come back after treatment. TKIs may be used in combination with other anticancer drugs as adjuvant therapy (treatment given after the initial treatment, to lower the risk that the cancer will come back).

Vaccine therapy

Vaccine therapy is a type of 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.

Other drug therapy

Lenalidomide is a type of angiogenesis inhibitor. It prevents the growth of new blood vessels that are needed by a tumor to grow.

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 child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Neuroblastoma



Low-Risk Neuroblastoma

Treatment of low-risk neuroblastoma may include the following:

Intermediate-Risk Neuroblastoma

Treatment of intermediate-risk neuroblastoma may include the following:

High-Risk Neuroblastoma

Treatment of high-risk neuroblastoma may include the following:

Stage 4S Neuroblastoma

There is no standard treatment for stage 4S neuroblastoma but treatment options include the following:

Recurrent Neuroblastoma

Patients First Treated for Low-Risk Neuroblastoma

Treatment for recurrent neuroblastoma that is found in one place in the body may include the following:

Treatment for recurrent neuroblastoma that has spread to other parts of the body may include the following:

Patients First Treated for Intermediate-Risk Neuroblastoma

Treatment for recurrent neuroblastoma that is found in one place in the body may include the following:

Recurrent neuroblastoma that has spread to other parts of the body is treated the same way as newly diagnosed high-risk neuroblastoma.

Patients First Treated for High-Risk Neuroblastoma

Treatment for recurrent neuroblastoma may include the following:

Because there is no standard treatment for recurrent neuroblastoma in patients first treated for high-risk neuroblastoma, patients may want to consider a clinical trial. For information about clinical trials, please see the NCI Web site.

Patients with Recurrent CNS Neuroblastoma

Treatment for neuroblastoma that recurs (comes back) in the central nervous system (CNS; brain and spinal cord) may include the following:

Treatments in Clinical Trials for Progressive/Recurrent Neuroblastoma

Some of the treatments being studied in clinical trials for neuroblastoma that recurs (comes back) or progresses (grows, spreads, or does not respond to treatment) include the following:

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with neuroblastoma. 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 child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

Changes to This Summary (08/28/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Images were added to this summary.

About This PDQ Summary



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This PDQ cancer information summary has current information about the treatment of neuroblastoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

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Clinical Trial Information

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." 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.

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