What is Neuroblastoma ?

Neuroblastomas are a type of cancer that develops in primitive nerve cells, called neuroblasts, which are left over in the body from the embryonic stage of development, before birth.
Neuroblastoma is rare. Only about 75 new cases are diagnosed in the UK each year. Overall it accounts for about 6 out of every 100 cases of cancer in children under the age of 15.
9 out of 10 neuroblastomas occur during the first 5 years of life, and 4 out of 10 are discovered before the age of one year. The condition is very rare indeed in older children. It is very slightly more common in boys than girls.

 

Neuroblastoma

Fewer than 100 children are diagnosed  each year with neuroblastoma in the UK. Most children who get this cancer are younger than five years old. Neuroblastoma is the second most common solid tumour in childhood and makes up 8% of the total number of children's cancers.

Neuroblastoma is a cancer of specialised nerve cells, called neural crest cells. These cells are involved in the development of the nervous system and other tissues.

Neuroblastoma can occur anywhere in the body, but it most often occurs in one of the adrenal glands in the abdomen (tummy). The adrenal glands are specialised glands which are found above the kidneys. They release hormones to maintain blood pressure, and enable us to respond to stress.

In some children, the neuroblastoma can occur in nerve tissue alongside the spinal cord in the neck, chest, abdomen or pelvis.

Causes of neuroblastoma

As with most cancers, the cause of neuroblastoma is unknown. It's not infectious and can't be passed on to other people.

Signs and symptoms

The first symptoms are often vague, such as loss of appetite, tiredness, and pain in the bones. Other symptoms vary, depending on where your child's neuroblastoma starts:

  • If the tumour is in the abdomen, your child’s tummy may be swollen and they may complain of constipation or have difficulty passing urine. Sometimes your child's blood pressure is high.

  • If the tumour affects the chest area, your child may be breathless and have difficulty swallowing.

  • If the tumour occurs in the neck, it is often visible as a lump and occasionally can affect breathing and swallowing.

  • Occasionally, there are deposits of neuroblastoma in the skin that appear as small, blue-coloured lumps.

  • If the tumour is pressing on the spinal cord, children may have weakness in the legs and walk unsteadily. If your child is not yet walking, you may notice reduced leg movements. They may also have constipation or difficulty passing urine.

  • Very rarely, children may have jerky eye and muscle movements, and general unsteadiness associated with the neuroblastoma.

How it is diagnosed

A variety of tests and investigations may be needed to diagnose a neuroblastoma. These include: blood, urine, or  bone marrow tests; x-rays, CT or MRI scans and mIBG scans. The tests are carried out to find the exact position of the neuroblastoma within the body and to see whether it has spread. This process is known as staging.

A specific type of urine test will also be done. Nearly all (nine out of 10) children with neuroblastoma will have substances called vanillylmandelic acid (VMA), or homovanillic acid (HVA), in their urine. Measuring the VMA and HVA in the urine can help to confirm the diagnosis. Your child will also have their VMA and HVA levels checked during and after treatment. The levels of these substances will fall if the treatment is working. As these chemicals are produced by the tumour cells, and can be used to measure tumour activity, they are sometimes known as tumour markers.

Most children will have an mIBG (meta-iodo-benzyl guanidine) scan . mIBG is a substance that is taken up by neuroblastoma cells. It is given by injection. Attaching a small amount of radioactive iodine to the mIBG enables the tumours to be seen by a radiation scanner. mIBG may also be used as a treatment.

A small sample of cells is usually taken from the tumour during an operation under a general anaesthetic. The cells are then examined under a microscope. This is called a biopsy. Other tests, collectively referred to as tumour biology are also carried out on these cells in the laboratory. These tests look at the chromosomes and 'biological markers' in the tumour cells. One of these markers' is called MYCN. If a certain amount of MYCN is present in the cells (known as MYCN amplification) this suggests the disease may be more aggressive. In this situation the treatment is more intensive.

Staging

The 'stage' of a cancer is a term used to describe its size and whether it has spread beyond its original site. Knowing the particular type and stage of the cancer helps doctors to decide on the best treatment for your child.

A commonly-used staging system for neuroblastoma is described below.

  • Stage 1 The cancer is contained within one area of the body (localised) and there is no evidence of it having spread. It can be completely removed by surgery , or there may be very small (microscopic) amounts of tumour left.

  • Stage 2A The cancer is localised and has not begun to spread, but cannot be completely removed by surgery.

  • Stage 2B The cancer is localised and has begun to spread into nearby lymph nodes.

  • Stage 3 The cancer has spread into surrounding organs and structures, but has not spread to distant areas of the body.

  • Stage 4 The cancer has spread to distant lymph nodes, bone, bone marrow, liver, skin or other organs. 

  • Stage 4S (also called special neuroblastoma). This is found in children under one year old. The cancer is localised (as in stage 1, 2A or 2B) and has begun to spread to the liver, skin or bone marrow.

A newer staging system is currently being developed by the International Neuroblastoma Risk Group (INRG). This system (described below) is beginning to be used more widely. It looks at whether or not certain 'image-defined risk-factors' are present. These risk factors can be detected by scans and help doctors to understand the extent of the disease. Your doctor can explain more about this.

Stage L1 The tumour is localised and has not spread into important areas (vital structures) nearby. It can be removed by surgery.

Stage L2 The tumour is localised but has 'image-defined risk factors' and can't be safely removed by surgery.

Stage M The tumour has spread to other parts of the body.

Stage MS The tumour has spread to the skin, liver and/or the bone marrow in children younger than 18 months old. 

If the cancer has spread to distant parts of the body, this is known as secondary , or metastatic cancer.

If the cancer comes back after initial treatment, this is known as recurrent cancer.

Treatment

The treatment of neuroblastoma depends on the age of the child, the size and position of the tumour, the tumour biology (including the MYCN status) and whether the neuroblastoma has spread.

Surgery

For tumours that have not spread (localised tumours), the treatment is usually surgery . If the tumour is at an early stage and there is no evidence that it has spread to the lymph nodes or other parts of the body, an operation to remove the tumour, or as much of it as possible, will be done.

In children with localised tumours, a cure is usually possible. However, if the tumour is classed as 'high-risk', due to the tumour biology results, further treatment will be needed. If the tumour is, at first, too large or in too difficult a position to remove safely, then chemotherapy will be given to shrink it before surgery.

Chemotherapy

If the tumour has already spread by the time of diagnosis, or is indicated as being high-risk by the tumour biology result, intensive chemotherapy is needed. Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. It is usually given as injections and drips (infusions) into a vein. Your child's specialist will discuss with you the type and amount of chemotherapy needed.

High-dose chemotherapy with stem cell rescue

If the neuroblastoma has spread to several parts of the body, or is high-risk with MYCN amplification, high‑dose chemotherapy with stem cell rescue  is used (after the initial courses of chemotherapy).

High doses of chemotherapy 'wipe out' any remaining neuroblastoma cells but they also wipe out the body's bone marrow, where blood cells are made. To prevent the problems that this causes, stem cells (blood cells at their earliest stages of development) are collected from your child through a drip before the chemotherapy is given. These stem cells are then frozen and stored. After the chemotherapy, the stem cells are given back to your child through a drip. They make their way into the bone marrow, where they grow and develop into mature blood cells over a period of 14–21 days.

Monoclonal Antibody Treatment

Monocolonal antiobodies can destroy some types of cancer cells while causing little harm to normal cells. A new monoclonal antibody treatment called anti-GD2 is currently being tested for people with high-risk neuroblastoma. Early reports from American research studies (2009) suggest this may be a promising therapy when given alongside other treatment. However, anti-GD2 has some unpleasant side effects and further studies need to be carried out before it can be considered a standard treatment. Anti-GD2 is not yet available in the UK, but this is currently under review. Your child's specialist will be able to tell you more.

Radiotherapy

External radiotherapy may be given if the neuroblastoma is high risk, or has spread to several parts of the body. This uses high-energy rays to destroy the cancer cells, while doing as little harm as possible to normal cells. External radiotherapy is given from a machine outside the body.

Internal radiotherapy may sometimes be given using radioactive mIBG. Radioactive mIBG is similar to the mIBG used in an investigation to diagnose a neuroblastoma, but uses higher doses of radioactivity to kill the cancer cells.