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NCI/PDQ^® Patients: Neuroblastoma Treatment (PDQ®)

National Cancer Institute
Ultima Vez Modificado: 19 de diciembre del 2012

TABLE OF CONTENTS

• General Information About Neuroblastoma

• Stages of Neuroblastoma

• Progressive/Recurrent Neuroblastoma

• Treatment Option Overview

• Treatment Options for Neuroblastoma
  • Low-Risk Neuroblastoma
  • Intermediate-Risk Neuroblastoma
  • High-Risk Neuroblastoma
  • Progressive/Recurrent Neuroblastoma

• To Learn More About Neuroblastoma

• Changes to This Summary (12/19/2012)

• Get More Information From NCI

• About PDQ®

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. Anatomy of the female urinary system showing the kidneys, adrenal glands, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis of each kidney. The urine flows from the kidneys through the ureters to the bladder. The urine is stored in the bladder until it leaves the body through the urethra.

Neuroblastoma most often begins during early childhood, usually in children younger than 5 years. It sometimes forms before birth but is usually found later, when the tumor begins to grow and cause symptoms. In rare cases, neuroblastoma may be found before birth by fetal ultrasound.

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

See the PDQ® summary on Neuroblastoma Screening for more information.

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

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

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

The most common 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 symptoms may be caused by neuroblastoma. Other conditions may cause the same symptoms. Check with your child's doctor if you see any of the following problems in your child:

• 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 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.
• Swelling of the legs, ankles, feet, or scrotum.

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.
• Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of certain substances. 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 substances homovanillic acid (HMA) and vanillyl mandelic acid (VMA) may 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.
• 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.
• 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.
• Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check 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.
• 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.
• 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.
• Immunohistochemistry study: A laboratory test in which a substance such as an antibody, dye, or radioisotope is added to a sample of cancer tissue to test for certain antigens. This type of study is used to tell the difference between different types of cancer.
• MIBG (metaiodobenzylguanidine) scan: A procedure used to find neuroendocrine tumors, such as neuroblastomas and pheochromocytomas. 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.

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 when diagnosed.
• Stage of the cancer.
• Where the tumor is in the body.
• Tumor histology (the shape, function, and structure of the tumor cells).
• Whether there is cancer in the lymph nodes.
• Whether there are certain changes in the chromosomes.
• How much time passed between diagnosis and when the cancer recurred.

Prognosis and treatment decisions 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.

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 infants, neuroblastoma may disappear without treatment. The infant is closely watched for symptoms of neuroblastoma. If 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 following tests and procedures may be used to determine the stage:

• 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.
• MIBG (metaiodobenzylguanidine) scan: A procedure used to find neuroendocrine tumors, such as neuroblastomas, that have spread to soft tissues or bones in other parts of the body. 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.
• 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:
  • Excisional biopsy: The removal of an entire lymph node.
  • Incisional biopsy: The removal of part of a lymph node.
  • Core biopsy: The removal of tissue from a lymph node using a wide needle.
  • Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid from a lymph node using a thin needle.

• 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): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• 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.
• 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.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

• Through tissue. Cancer invades the surrounding normal tissue.
• Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
• Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone 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 stage 2A and 2B.

• Stage 2A: The tumor is in only one area and all of the tumor that can be seen cannot be completely removed during surgery.
• Stage 2B: The tumor is in only one area and all of the tumor that can be seen may be completely removed during surgery. Cancer cells are found in the lymph nodes near the tumor.

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 stage 4 and stage 4S.

• In stage 4, the tumor has spread to distant lymph nodes, the skin, or other parts of the body.
• In stage 4S, the following are true:
  • the child is younger than 18 months; and
  • the cancer has spread to the skin, liver, and/or bone marrow; and
  • the tumor is in only one area and all of the tumor that can be seen may be completely removed during surgery; and/or
  • cancer cells may be found in the lymph nodes near the tumor.

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 3 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 difficult to cure.

Progressive/Recurrent Neuroblastoma

Progressive neuroblastoma is cancer that has progressed (continued to grow) during treatment. 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.

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:

• Medical oncologist.
• Hematologist.
• Pediatric surgeon.
• Radiation oncologist.
• Endocrinologist.
• Neurologist.
• Neuropathologist.
• Neuroradiologist.
• Pediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.

Children who are treated for neuroblastoma may be at higher risk for 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:

Surgery

Surgery is usually used to treat neuroblastoma. Depending on where the tumor is and whether it has spread, 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.

Neuroblastoma is sometimes treated with radioactive iodine (RAI) therapy, which carries radiation directly to tumor cells. RAI collects in certain kinds of tumor cells, killing them with the radiation that is given off. Before a full treatment dose of RAI is given, a small test-dose is given to see if the tumor takes up iodine.

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.

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.

Watchful waiting

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

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. Monoclonal antibody therapy is one type of targeted therapy being studied in the treatment of neuroblastoma.

Monoclonal antibody therapy is a cancer treatment 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 deliver drugs, toxins, or radioactive material directly to cancer cells.

High-dose chemotherapy and radiation therapy with stem cell transplant

High-dose chemotherapy and radiation therapy with stem cell transplant is a way of giving high doses of chemotherapy and radiation therapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor 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.

Other drug therapy

13-cis retinoic acid is a vitamin-like drug that slows the cancer's ability to make more cancer cells and changes how these cells look and act.

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

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your child's doctor for clinical trials that are not listed here but may be right for your child.

Low-Risk Neuroblastoma

Treatment of low-risk neuroblastoma may include the following:

• Watchful waiting alone for certain infants.
• Surgery followed by watchful waiting.
• Surgery followed by combination chemotherapy, when serious health problems occur.
• Radiation therapy to treat tumors that are causing serious health problems and do not respond quickly to chemotherapy.

Intermediate-Risk Neuroblastoma

Treatment of intermediate-risk neuroblastoma may include the following:

• Surgery alone.
• Surgery followed by chemotherapy. Sometimes a second surgery is needed.
• Watchful waiting alone for certain infants.
• Surgery followed by chemotherapy. Radiation therapy may given to treat tumors that are causing serious health problems and do not respond quickly to surgery and chemotherapy.
• Chemotherapy followed by surgery.
• Radiation therapy to treat tumors that are causing serious problems and do not respond quickly to chemotherapy.

High-Risk Neuroblastoma

Treatment of high-risk neuroblastoma may include the following:

• Combination chemotherapy followed by surgery to remove as much of the tumor as possible, followed by high-dose chemotherapy and stem cell transplant.
• Radiation therapy to the tumor site and, sometimes, if needed, to other parts of the body with cancer.
• 13-cis retinoic acid after recovery from previous treatment.
• A clinical trial of new regimens of chemotherapy and radioactive iodine therapy followed by more chemotherapy, stem cell rescue, and external-beam radiation therapy.
• A clinical trial of chemotherapy and stem cell transplant followed by 13-cis retinoic acid with or without monoclonal antibody therapy and biologic therapy.

Progressive/Recurrent Neuroblastoma

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:

• Surgery to remove the tumor followed by radiation therapy.
• Radiation therapy to the brain and spinal cord.
• Surgery, radiation therapy, and chemotherapy followed by targeted therapy with a radioactive substance linked to a monoclonal antibody.

Patients First Treated for Low-Risk Neuroblastoma

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

• Surgery followed by watchful waiting or chemotherapy.
• High-dose chemotherapy, stem cell transplant, and 13-cis retinoic acid.

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

• Watchful waiting.
• Surgery followed by chemotherapy.
• High-dose chemotherapy, stem cell transplant, and 13-cis retinoic acid.
• A clinical trial of a new treatment.

Patients First Treated for Intermediate-Risk Neuroblastoma

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

• Surgery, with or without chemotherapy.
• A clinical trial of a new treatment.

For recurrent neuroblastoma that has spread to other parts of the body, treatment is usually high-dose chemotherapy, stem cell transplant, and 13-cis retinoic acid.

Patients First Treated for High-Risk Neuroblastoma

Treatment for recurrent neuroblastoma in patients first treated for high-risk neuroblastoma may include the following:

• A second course of high-dose chemotherapy and stem cell transplant.
• Chemotherapy with one or more anticancer drugs.
• Radioactive iodine therapy to relieve symptoms and improve quality of life.

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.

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

To Learn More About Neuroblastoma

For more information from the National Cancer Institute about neuroblastoma, see the following:

• Neuroblastoma Home Page
• Neuroblastoma Screening
• Drugs Approved for Neuroblastoma
• Targeted Cancer Therapies
• Understanding Cancer Series: Targeted Therapies (Advances in Targeted Therapies )
• New Approaches to Neuroblastoma Therapy (NANT)

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

• What You Need to Know About Cancer
• Childhood Cancers
• CureSearch for Children's Cancer
• Late Effects of Treatment for Childhood Cancer
• Adolescents and Young Adults with Cancer
• Young People with Cancer: A Handbook for Parents
• Care for Children and Adolescents with Cancer
• Understanding Cancer Series: Cancer
• Cancer Staging
• Coping with Cancer: Supportive and Palliative Care
• Questions to Ask Your Doctor About Cancer
• Cancer Library
• Information for Survivors/Caregivers/Advocates

Changes to This Summary (12/19/2012)

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.

Editorial changes were made to this summary.

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