Neuroblastoma Treatment (PDQ®)

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.

Figure

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.

The gene mutation that increases the risk of neuroblastoma is sometimes inherited (passed from the parent to the child). In patients with this gene mutation, neuroblastoma usually occurs at a younger age and 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.
• Hormone test: A procedure in which a blood sample is checked to measure the amount of hormones released into the blood by the adrenal medulla. 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.

  

  Figure

  Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the child’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.

• 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.

  

  Figure

  Computed tomography (CT) scan of the abdomen. The child lies on a table that slides through the CT scanner, which takes x-ray pictures of the inside of the abdomen.

• 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.

  

  Figure

  Abdominal ultrasound. An ultrasound transducer connected to a computer is pressed against the skin of the abdomen. The transducer bounces sound waves off internal organs and tissues to make echoes that form a sonogram (computer picture).

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.
• Where in the body the tumor started.
• 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.

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:

• Lumbar puncture: A procedure used to collect cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that the cancer has spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.
• Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells. One of the following types of biopsies may be done:

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  Excisional biopsy: The removal of an entire lymph node.

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  Incisional biopsy: The removal of part of a lymph node.

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  Core biopsy: The removal of tissue from a lymph node using a wide needle.

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  Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid from a lymph node using a thin needle.

• X-rays of the chest, bones, and abdomen: 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.
• Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones with cancer and is detected by a scanner.

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:

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.

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 who are experts 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:

• Pediatric surgeon.
• Radiation oncologist.
• Endocrinologist.
• Neurologist.
• Neuropathologist.
• Neuroradiologist.
• Pediatrician.
• Pediatric nurse specialist.
• Social worker.
• Child life professional.
• Rehabilitation specialist.
• Psychologist.

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:

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 website.

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.

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.

Low-Risk Neuroblastoma

Treatment of low-risk neuroblastoma may include the following:

• Surgery followed by observation.
• Chemotherapy with or without surgery, for some patients.
• Observation alone for infants who do not have signs or symptoms of neuroblastoma. More studies are needed before this is considered a standard treatment.
• A clinical trial of treatment guided by the tumor's response to treatment and whether there are certain changes in the tumor cells.

Intermediate-Risk Neuroblastoma

Treatment of intermediate-risk neuroblastoma may include the following:

• Chemotherapy with or without surgery.
• Surgery alone for infants.
• Observation alone for certain infants.
• Radiation therapy to treat tumors that are causing serious problems and do not respond quickly to chemotherapy or surgery.
• Radiation therapy for tumors that do not respond to other treatment.
• A clinical trial of treatment guided by the tumor's response to treatment and whether there are certain changes in the tumor cells.

High-Risk Neuroblastoma

Treatment of high-risk neuroblastoma may include the following:

• A regimen of combination chemotherapy, surgery, stem cell rescue, radiation therapy, and anti-GD2 ch14.18 with interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), and isotretinoin.
• A clinical trial of chemotherapy combined with mIBG, followed by surgery, more chemotherapy, stem cell rescues, radiation therapy, and isotretinoin.
• A clinical trial of chemotherapy and stem cell rescue followed by isotretinoin with or without monoclonal antibody therapy and biologic therapy.

Stage 4S Neuroblastoma

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

• Observation with supportive care for certain patients who have favorable tumor biology and do not have signs or symptoms.
• Chemotherapy, for children who have signs or symptoms of neuroblastoma or unfavorable tumor biology, or for very young infants.
• A clinical trial of treatment guided by the tumor's response to treatment and whether there are certain changes in the tumor cells.

Recurrent Neuroblastoma

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

• Surgery followed by observation or chemotherapy.
• Chemotherapy that may be followed by surgery.

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

• Observation for certain infants.
• Chemotherapy.
• Surgery followed by chemotherapy.
• Combination chemotherapy.

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

• Surgery that may be followed by chemotherapy.

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

Treatment for recurrent neuroblastoma may include the following:

• Combination chemotherapy.
• mIBG therapy to relieve symptoms and improve quality of life. It may be given alone or in combination with other therapy, or after stem cell rescue.
• A second course of high-dose chemotherapy and stem cell rescue.

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 website.

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

• Surgery to remove the tumor in the CNS followed by radiation therapy.
• A clinical trial of a new therapy.

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:

• Combination chemotherapy and ch14.18 monoclonal antibody therapy.
• Lenalidomide and ch14.18 monoclonal antibody therapy with or without isotretinoin.
• Vaccine therapy.
• A tyrosine kinase inhibitor (crizotinib) with or without combination chemotherapy.

Check the list of NCI-supported 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 website.

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