Neuroblastoma

Neuroblastoma is a cancerous tumor that begins in nerve tissue of young children. Abnormal nerve cells may be present before birth, but the diagnosis isn’t made until the cells begin to multiply, forming a tumor. Neuroblastoma is most commonly diagnosed in children less than 5 years of age and is very rare after the age of 10.

A neuroblastoma tumor usually begins in the abdomen, especially in the tissues of the adrenal glands, which sit on top of the kidneys but also may begin in nerve tissue in the neck, chest, or pelvis. Neuroblastoma cancer cells can spread (metastasize) to other areas of the body, including the lymph nodes, liver, bones, and bone marrow.

Neuroblastoma usually begins in the abdomen, especially in the tissues of the adrenal glands, which sit on top of the kidneys, but may also begin in nerves tissues in the neck, chest or pelvis. These tumors often spread (metastasize) to other areas of the body, including the lymph nodes, liver, bones and bone marrow. Nearly 70 percent of children with neuroblastoma will have metastatic disease at diagnosis.

Neuroblastoma symptoms can vary greatly, depending on the size and location of the tumor and whether or not the tumor has spread.

Common signs and symptoms of neuroblastoma include:

• An abdominal mass, either felt during an examination or seen as a swollen abdomen
• Enlarged lymph nodes in the neck
• Swelling and bruising of the area around the eyes
• Unexplained fevers, bone pain or limping caused by bone or bone marrow involvement
• Weakness or paralysis caused by compression of the spinal cord by tumor
• Weight loss or poor appetite
• Uncontrolled eye or leg movements caused by an autoimmune response to the tumor
• High blood pressure, due to compression of the kidney by the tumor
• High blood pressure, increased heart rate and flushing due to a substance produced by the tumor
• Diarrhea caused by a substance produced by the tumor

Keep in mind that neuroblastoma symptoms may resemble other, more common conditions or medical problems. Always consult your child's physician for a diagnosis.

In the U.S., about 650 children are diagnosed with neuroblastoma each year. Neuroblastoma usually occurs before a child is 5 years of age — it is the most common tumor found in children younger than 1 year old. Neuroblastoma is rare in children older than 10 years; however, it does occur occasionally in adults.

The cause of neuroblastoma is not completely understood. It is likely that neuroblastoma develops from an early form of a nerve cell (called a neuroblast), found in the fetus, which grows abnormally due to a genetic mutation inside the cell. In most cases of neuroblastoma, scientists still are trying to identify this genetic abnormality and what causes it.

In rare cases, neuroblastoma is caused by an inherited alteration in a specific gene. The gene most commonly affected is the ALK gene, a protein coding gene. Hereditary neuroblastoma accounts for only 1 to 2 percent of cases of neuroblastoma. Because neuroblastoma often occurs very early in childhood, research has been done to find any links between maternal environmental exposures and tumor development. No such associations have been found.

Your child’s doctor will perform a complete medical and physical examination. In addition, your child’s physician may order one or more of the following tests:

• Imaging studies
• Metaiodobenzylguanidine (MIBG) scan
• Computerized tomography scan (CT or CAT scan)
• Magnetic resonance imaging (MRI)
• Bone scan
• Bone marrow biopsy and/or aspiration
• Urine test
• Biopsy
• Blood tests

Neuroblastoma tumor risk groups

Diagnosing neuroblastoma also involves determining the neuroblastoma risk group, which will help your child’s doctor determine neuroblastoma treatment options and prognosis. Children with neuroblastoma are divided into three risk groups depending on their age, the stage of the tumor and certain biological factors of the tumor. The three risk groups are low, intermediate and high.

Staging the tumor

Staging describes the size of the tumor and whether or not it has spread. The most commonly used staging system is the International Neuroblastoma Staging System:

• Stage 1 — localized tumor that is completely surgically removed at diagnosis
• Stage 2 — localized tumor that cannot be completely surgically removed at diagnosis. Lymph nodes on the same side of the tumor may have tumor cells present
• Stage 3 — large tumor that has spread across the middle of the body and cannot be surgically removed at diagnosis
• Stage 4 — tumor of any size that has metastasized (spread) to distant lymph nodes, bone marrow, bone or livers
• Stage 4s — special stage that applies only to a child less than 1-year-old. Small, localized tumor that has metastasized (spread) to liver, skin and/or bone marrows

Your child’s physician will determine a specific course of neuroblastoma treatment for your child based on the tumor risk group and other factors. Neuroblastoma treatment may include:

• Surgery
• Chemotherapy
• Radiation
• Stem cell transplant
• Iologic therapy
• MIBG Therapy
• Immunotherapy

These neuroblastoma treatments can be used alone or in combination depending on the neuroblastoma risk group.

Low-risk neuroblastoma

Patients with low-risk neuroblastoma usually require only surgery and/or observation. Occasionally, a patient with a low-risk tumor will need chemotherapy (or radiation treatment) to shrink a tumor before it is removed.

Intermediate-risk neuroblastoma

Patients with intermediate-risk disease are treated with chemotherapy to shrink the tumor, before the tumor can be surgically removed. The actual medications used are chosen to try to minimize side effects, both during treatment and in the future.

High-risk neuroblastoma

High-risk neuroblastoma is an aggressive disease that is treated with a combination of therapies including chemotherapy, surgery, radiation, stem cell transplant, biologic therapy, MIBG therapy, and immunotherapy.

Because neuroblastoma is rarely seen in adults, it is important that your child receive care from an experienced team of pediatric specialists who focus exclusively on treating childhood cancers. Neuroblastoma specialists and surgeons in the Neuroblastoma Program at Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center are known for treating children with the most complex cases (including relapsed or refractory neuroblastoma), as well as for their expertise in delivering specialized treatments, including MIBG therapy and stem cell transplantation.

Your child may be eligible to participate in one of the Neuroblastoma Program’s current clinical trials. In addition to launching our own clinical trials, we also offer the most Phase I studies in New England for children whose disease has recurred through the Children's Oncology Group and the New Approaches to Neuroblastoma Therapy (NANT) consortium.

Our current research efforts focus on improving established neuroblastoma therapies, studying the genetic causes of the disease and developing novel therapies.

Reducing late effects

Children with low- and intermediate-risk neuroblastoma often can be cured with surgery alone, or surgery and chemotherapy. Because of the risk of physical, psychological, social, intellectual and other late effects, we are constantly working to decrease the intensity of treatment as much as possible while still providing the best cure rates.

Recent neuroblastoma treatment developments

Recent developments in the treatment of neuroblastoma have included identification of several genetic findings in the tumors that can predict either a favorable or unfavorable prognosis. These tests have provided valuable information indicating which tumors need to be treated aggressively and which tumors require little treatment beyond surgical removal.

In addition to these tests, our center our scientists are currently studying how to use high-dose therapy in combination with stem cell transplantation to treat neuroblastoma. Dana-Farber/Boston Children’s Pediatric Stem Cell Transplant Center is one of only eight institutions around the U.S. investigating the use of umbilical cord transplantation. Also being studied is a new method for preventing graft-versus-host disease, a serious complication that occurs when transplanted cells don’t recognize the tissues and organs of the recipient's body and react against the recipient's tissue. This treatment approach may dramatically increase the pool of potential donors for each patient. Another promising area of research is developing treatments that allow doctors to use a patient's own stem cells to overcome neuroblastoma.

Attacking the genetic cause

Researchers at Dana-Farber/Boston Children’s have published some of the early work on the association between neuroblastoma and the ALK gene. Together with researchers at Children’s Hospital of Philadelphia, we are working on therapies that target this gene and may improve treatment for neuroblastoma.

Advanced radiation treatment for neuroblastoma

Nuclear medicine physicians and scientists are an integral part of the Dana-Farber/Boston Children’s team's MIBG treatment for children with relapsed neuroblastoma (cancerous tumors that originate in the nerve tissues). The treatment, which uses a radioactive compound to kill tumor cells, is available in only a handful of major medical centers in North America. Dana-Farber/Boston Children’s is the only center in New England to offer this therapy.