Basic Facts

Neuroblastoma is a cancerous tumor that begins in the nerve tissue of infants and young children. As a cancer of the sympathetic nervous system – or the message network between the brain and other parts of the body, development typically begins on or near the adrenal glands in the abdomen, but also originates in the nerve tissue in the neck, head, chest, and pelvis. While Neuroblastoma involves systems and networks in the body that use and work with the brain, brain tumors as a result of Neuroblastoma are uncommon.

It is believed that in many cases, the abnormal cells begin development before birth, and one-third of the cases are diagnosed before the loved one reaches their first birthday. Unfortunately the remaining cases continue to spread in the body (metastasize), and only becomes noticeable to parents and doctors when the spreading disease causes pain or discomfort to the child. Most cases are officially diagnosed before a child’s 5th birthday.

Statisics

• Approximately 650 new cases of Neuroblastoma are diagnosed each year, making it the leading cancer diagnosis in kids under 1, and the third most common from of Cancer in our children. Boys are slightly more likely to be diagnosed with Neuroblastoma than Girls.
• Neuroblastoma accounts for 7% of the diagnosis of pediatric Cancer, but 15% of the deaths.
• Average age of diagnosis is 9 months old.
• Because of the difficulty in diagnosis, 70% of diagnosed cases have spread to multiple parts of the body.
• 2% of Neuroblastoma cases involve multiple siblings in the same family.

Cause

There is a reason that there are very few cases of Neuroblastoma. The causes are a case of many factors lining up perfectly for uncontrolled growth to begin.

When an unborn baby is developing, the cells that become the nerve cells, the adrenal gland and part of the brain (medulla) are called Neuroblasts. As they mature, Neuroblasts develop, they take on the form of the nerve cells, the adrenal gland, and the medulla.

Occasionally, these cells are still present after birth. In some cases, these cells would eventually mature into normal nerve cells. In other cases, these Neuroblasts would continue to divide and form tumors. These suddenly stop growing, and disappear within 12-18 months of age. This is called Stage 4S. The likelihood of this spontaneous disappearance of reduces significantly with age. Uncontrolled Neuroblasts over time form Neuroblastoma. Staging, or involvement of the disease depends on several factors, discussed below.

So WHAT causes the cells not to mature? As Neuroblasts cells develop, abnormalities in it’s makeup, or it’s chromosomes, cause the cells to continue growing and not mature. Some is believed to be resulting by some form of inherited genetics, but most cases are not related to genetics. Less than 2% of all Neuroblastoma cases occur in the same family. Most cases are the result of mutations after birth.

WHY these mutations occur initially is unknown, although there is no evidence that environmental situations have any relationship. There is some evidence that a combination of mutations prior to birth and just after birth cause these mutations, but much more research is needed to identify what starts the mutation in the first place. Additional details are discussed in Neuroblastoma 301.

Symptoms

Catching Neuroblastoma early is very difficult and often indistinguishable from other more common, less involved illnesses. It is often called the “great mimicker”. While most cases initiate in the abdomen (with the majority of those beginning on the adrenal gland), the disease can initiate in other areas of the body, and thus present completely differently. Initial symptoms may include fatigue or loss of appetite, but as the disease progresses, symptoms will depend on what the tumors have attached to. Some common symptoms include:

• Feeling of constantly being “full”
• Fever
• Limping, complaining of pain when walking, loss of range of motion in arms
• Bulging, or protruding eyes, black circles around eyes
• Headaches
• Constipation
• Persistent diarrhea, nausea
• Rapid Heartbeat, high blood pressure
• Reddening, small “bruises”
• Trouble breathing or swallowing

These symptoms give you an idea why Neuroblastoma is difficult to diagnose. Symptoms can indicate countless other illnesses and diseases. PLEASE consult your physician if your loved one does not appear “right”. It is a difficult process, and you need to be persistent until your child’s symptoms can be definitively explained.

Diagnosis

Once symptoms are present, there are multiple tests that will take place to determine if Neuroblastoma is present, and where it has spread, and the makeup of the cells. Tests often require sedation or prolonged length of time with no movement. Emotionally, it is draining on the parents and families, adding to the stress of testing. It’s difficult, but tests are vital in determining what to do next. Some likely tests include:

Blood and Urine Tests

Urine tests will check for certain chemicals that can be tied back to Neuroblastoma in 90% of incidences (called catecholamines). Blood tests may be done to check blood count levels as well as organ function.

X-Rays

A standard X-Ray is done to help identify locations of tumors. This is used primarily for looking at the (skull), lungs, and lymph nodes.

Computed Tomography CT Scan

A CT Scan is helpful in finding tumors in the abdomen, chest, and pelvis areas. It is effectively a specialty X-Ray, that helps find masses that are not visible with a standard X-Ray. Your loved one will be asked to drink a fluid that helps the scans effectiveness. The sensitivity of the scans requires your loved one to main on the scan table longer, but CT is more effective in detailing tumors in your child’s body. Keep in mind that a small amount of these tests are safe, but since the CT is based on X-rays (which is radiation), dozens and dozens of these tests may impact your child.

Magnetic Resonance Imaging (MRI)

An MRI uses different techniques in finding tumors in the body. It is used most often in finding tumors in the brain or in the spinal column. It is based on radio waves, not X-Rays, so radiation is not a factor. MRI’s are an effective test, but are difficult on the child. It’s vital to remain motionless for extended periods of time. The test takes place in a narrow tube with loud thumping noises consistently heard. Sedatives or other drugs that help your loved onesleep may be used to help, including anesthesia.

Bone Marrow Aspirate (BMA)

This test helps identify the presence of Neuroblastoma in the bone marrow, another common place of disease spreading. A small amount of bone marrow tissue and fluid is removed. In most cases, the test is done on each pelvis, but some prefer to test 4 locations. Since there is a level of discomfort, a sedative is often given to your loved one prior to the test, which aids in “forgetting” the procedure. This test is important in identifying any disease in the marrow, as well as estimating levels of the disease present.

Bone Scan

As the name indicates, a bone scan looks for tumors on the bones. A radioactive solution is injected into your child’s bloodstream, and upon scanning, shows any “damaged” areas of the bone. A professional identifies differences between Cancerous lesions and other damage (fractures, arthritis, etc). This test also requires your loved one to be still on the scanning table for an extended period of time, and can be difficult.

MIBG Scan

The MIBG scan is the most effective test in determining location of tumors and disease. MIBG attaches to the Neuroblastoma cells, and helps doctors effectively manage growth or reduction, as well as identifying presence of Neuroblastoma cells. A radioactive contrast is injected into your child’s blood stream, followed by a scan to see where the MIBG is located. You may hear the term “light up” when referring to the MIBG scan. This is indicative of the MIBG appearing bright on the scan when attached to the Neuroblastoma cells. This is typically the baseline test for Neuroblastoma children.

Ultrasound

An Ultrasound uses sound waves to create a picture, typically pictures of organs or large masses. It is an easy test to conduct, and a painless test on your loved one.

Tumor biopsies

A tumor biopsy is the most conclusive method of testing for Neuroblastoma, as well as determining the makeup of the tumor, and the makeup of the Neuroblastoma cells. This can be done either while the mass is still in the body, or after the mass has been extracted. This is an important step in determining the makeup, or Histology of the disease.

Staging

If it is found that your loved one has Neuroblastoma, an important factor in determining prognosis is the stage of the disease. The stage is based on where the disease has spread, as well as the makeup of the disease. Most centers use the International Neuroblastoma Staging System, and will be used regardless of your medical center:

Stage 1

The cancer is localized (hasn't spread). It is on one side of the body. All visible tumor is totally removed by surgery. Examination of the tumor's edges under the microscope may show some cancer cells. Lymph nodes enclosed within the tumor may contain neuroblastoma cells, but lymph nodes outside of the tumor should be free of cancer.

Stage 2A

The cancer is localized, but because of its size, location, or relationship to other organs, most but not all of the tumor can be removed by surgery. It is on one side of the body. Lymph nodes enclosed within the tumor may contain neuroblastoma cells, but lymph nodes outside of the tumor should be free of cancer.

Stage 2B

The cancer is localized, and may or may not be able to be totally removed by surgery. It is on one side of the body. Nearby lymph nodes outside the tumor contain neuroblastoma cells, but the cancer has not spread to lymph nodes on the other side of the body or elsewhere.

Stage 3

The cancer cannot be completely removed by surgery or it has crossed the midline (defined as the spine) to the other side of the body. It may or may not have spread to nearby lymph nodes,

  Or, it is on one side of the body but has spread to lymph nodes that are relatively nearby but on the other side of the body.

  Or, it is in the middle of the body and growing toward both sides and cannot be completely removed by surgery.

Stage 4

The cancer has spread to distant sites such as distant lymph nodes, bone, liver, skin, bone marrow, or other organs. But the child does not meet criteria for stage 4S.

Stage 4S - (also called "special" neuroblastoma)

The child is younger than 1 year old. The cancer is on one side of the body and is localized. It may have spread to lymph nodes on the same side of the body but not to nodes on the other side. The neuroblastoma has spread to the liver, skin, and/or the bone marrow. However, no more than 10% of marrow cells may be cancerous, and imaging studies do not show bone damage.

Progressive/Recurrent

Progressive disease is cancer that has progressed during treatment. Our son Nicholas was considered Progressive following his treatment plan. Recurrent disease is cancer that returns after it has been treated. It may come back in the area where it first started or in another part of the body.

Treatments

Treating Neuroblastoma depends on the makeup of the disease, where the disease has originated and spread to, and the age of your loved one. These factors dictate which risk group your loved one will be in, and what treatment plan will be used. Placement in a risk group identifies Your physician will review treatment options during your loved ones treatment plan, but here’s an overview of standard and advanced treatments. For more detailed information on treatments, please check Neuroblastoma 301. For additional information on treatments, or places to look for more information, please Contact us.

Standard Treatments

Surgery

Most cases of Neuroblastoma result in surgery. Surgery may occur at the outset of treatment, or it may be necessary to wait until the mass shrinks as a result of other treatments (chemotherapy). In some cases, surgery may not be possible. If the mass cannot be removed, then a biopsy will be done to determine the make-up of the mass.

Surgery is usually a serious procedure requiring anesthesia and recovery time. It’s important that you feel comfortable with the surgeon, understand the procedure, and any risks associated with surgery

Chemotherapy

Chemotherapy is used to stop the growth of the caner cells by either killing the cells, or by stopping them from dividing. Chemo enters the bloodstream, and is sent throughout the body (systemically). Varying strengths of dosage and combinations are used based on diagnosis and stage of disease.

Unfortunately, chemotherapy doesn’t target Cancer cells only – “good cells” are also attacked, resulting in the common side effects seen with Cancer. Dramatic reduction in blood counts (White Blood Cells, Hemoglobin, Platelets) are to be expected. This will be monitored by your oncologists during treatments. Please see the Family Support section for more information on side effects and management.

In most cases, an Access line will be inserted to minimize the number of “pokes”, and make the process of treatments easier on your loved one. See the Family Support for more information on Access lines.

Radiation

Radiation is a therapy using high-energy x-rays or other types of radiation to kill cancer cells. External Radiation uses a machine outside the body that is calibrated to the impacted areas, and sent toward the cancer cells. Treatments are usually administered daily over multiple weeks.

Typical treatments are usually done outpatient, and require a short amount of time daily. Discomfort is likely, but considered less invasive that other treatments.

Radiation is most effective when areas of disease can be pinpointed to a specific area. Your team of physicians will identify radiation as a viable option in your loved one’s treatment plan.

Advanced Treatments

Stem Cell Transplant

Stem Cell transplant is similar to a bone marrow transplant. A child is given high doses of chemotherapy, which is designed to eliminate all bone marrow to the point assistance is needed to “kick start” the body’s blood making machine (the bone marrow). Bone Marrow transplants use the marrow of a “donor” that matches the patient. This is introducing a foreign object into the child’s body, which causes multiple complications. Stem Cell transplants eliminate many of the complications by using the child’s own stem cells (precursors to their own marrow) as the kick start. The stem cells are at a point in development where the Neuroblastoma cells have not attached yet.

Transplant is a serious procedure with risks. Please see Neuroblastoma 301for more details.

Monoclonal Antibody

Your loved ones immune system creates antibodies that attack germs and “foreign objects”. Because tumors are made up of cells made from your own body, your immune system does not attack it.

In order to get your immune system to attack the cancer cells, a foreign body needs to attach to the cancer. That is the basis of this treatment. A foreign substance designed to attach specifically to Neuroblastoma cells is created in a laboratory. It is then delivered intravenously, circulating through the body, and attaching to Neuroblastoma cells. The immune system attacks the foreign body, and in theory, the Neuroblastoma cell it is attached to.

Various versions of this treatment are delivered nationwide. There are also risks and side effects with this treatment. See Neuroblastoma 301 for more details.

13-cis Retinoic Acid (Accutane)

Accutane is commonly used to combat Acne, but is also used as a method to battle residual Neuroblastoma disease, and the chances of relapse. It is designed to limit the ability of the Neuroblastoma cells to grow.

The drug is extremely sensitive to light and air, and is administered to you loved one in a large pill. Taking the pill is often a challenge for children, but other side effects can be considered minimal.

Prognosis

Prognosis of kids with Neuroblastoma has several variables.

Age

Children under the age of 1 with advanced diseased and favorable disease characteristics (makeup of the Neuroblastoma genes) have a high likelihood of long term, disease free survival. The sooner the disease is found, the better the survival

Disease Stage

Progression of the Disease (which stage) is a major indicator of prognosis. High Risk (Stage 4) has unfavorable prognosis, while Stage 1 has a relatively positive one. Unfortunately, by the time it is diagnosed, 70% of the cases are Stage 4.

Biologic Factors

The makeup of the Neuroblastoma cell helps determine how aggressive the disease is likely to be. A Neuroblasts ability to control growth, and mature normally can be measured on specific markers in the makeup.

The 5-year survival, or the percentage of children surviving 5 years after diagnosis is favorable in the low and intermediate risks.

Risk	Survival
Low	95%, 5-year survival
Intermediate	85%, 5-year survival
High	30%, 5-year survival
Progressive/ Relapse	‹ 10%, 5-year survival

Source: NIH