Neuroblastoma

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

Neuroblastoma is the most common form of embryonal tumour. Embryonal tumours are characterised by the proliferation of tissue that is normally only seen in the developing embryo. They are mainly seen in very young children.

The causes of neuroblastoma are not known.

Incidence

Neuroblastoma accounts for 6% of childhood cancer registrations in the UK, with around 95 diagnoses annually.

As with all embryonal tumours, neuroblastoma is most common in children under the age of five years and extremely rare after the age of 10 years.

The incidence of neuroblastoma is highest in the under ones – it is the most frequent single type of cancer in the first year of life, accounting for one fifth of cancers in this age group.

Neuroblastoma is slightly more common in boys than in girls, by a ratio of 6:5.

Survival

Neuroblastoma has one of the lowest survival rates of all childhood cancers, with only 67% of patients surviving to five years.

Neuroblastoma is also one of the few types of cancer for which survival differs significantly between the sexes – boys have a worse outlook than girls.

Infants have a better outlook than older children: those diagnosed before the age of one have five-year survival of 83% compared to only 43% for those in the 1-4 year age group.

The first symptoms of neuroblastoma are generally vague, such as loss of appetite, tiredness and pain in the bones.

Other symptoms vary, depending on where the child’s neuroblastoma starts:

• If it is in their abdomen, their tummy may be swollen and they may complain of constipation or difficulty passing urine
• If the tumour is in the chest or neck area, the child may be breathless and have difficulty swallowing
• Occasionally there may be deposits of neuroblastoma in the skin that appear as small, blue-coloured lumps
• If the tumour is pressing on the spinal cord, it may cause weakness in the legs.

A variety of tests and investigations may be needed to diagnose a neuroblastoma cancer. These include blood, urine or bone marrow tests, X-rays, CT or MRI scans and mIBG scans (see below). These tests confirm the diagnosis and help doctors to determine the best way to treat the tumour.

mIBG is a substance that is taken up by neuroblastoma cells. It is given by injection with a small amount of radioactive iodine attached to enable the tumours to be seen by a radiation scanner. mIBG may also be used to deliver treatment directly to the tumour.

Tumour cells are taken by biopsy to look at the chromosomes and ‘biological markers’ and help inform the type and intensity of treatment required. If a certain level of a marker called MYCN is detected it indicates that the tumour is high-risk and that treatment needs to be more intensive.

Staging of Neuroblastoma

The stage of a cancer describes how far it has grown or spread. The stage is important because it helps determine the best treatment. There are four main stages of neuroblastoma cancers:

Stage 1 means the tumour is in one area of the body and hasn’t spread. It can be completely removed with surgery.

Stage 2 is divided into 2A and 2B. In 2A, the tumour can’t be completely removed with surgery because of its size or position, but there are no cancer cells in any lymph nodes. In stage 2B, it may or may not be possible to completely remove the tumour, but it has spread to nearby lymph nodes.

Stage 3 means that the tumour can’t be completely removed with surgery and there is either tumour on both sides of the body (either side of the spine) or there is tumour on one side of the body and lymph nodes containing cancer cells on the other.

Stage 4 means that the cancer has spread to parts of the body that are some distance from where it started.

Stage 4S is a special case, as it has a better outlook than other stages. Stage 4S means the child is younger than one year at diagnosis. The tumour may have spread to the liver or skin, but not to the bones. And no more than 10% of cells in the bone marrow are neuroblastoma cells.

Children with stage 4S disease almost always get better with very little treatment or none at all. These tumours either regress spontaneously or after chemotherapy success, which is only given if the tumour is causing symptoms. They disappear completely or develop into a non-cancerous (benign) tumour, called a ganglioneuroma. Many of these children, after their initial diagnostic tests and staging investigations, will just need careful monitoring for some years.

A newer staging system has been developed by the International Neuroblastoma Risk Group (INRG). This system looks at whether or not certain ‘image-defined risk factors’ are present in a neuroblastoma tumour before treatment. These risk factors can be detected by scans and help doctors understand the extent of the disease.

Stage L1 – the tumour is localised and has not spread into 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.
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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.

For early-stage tumours which have not spread, surgery alone may be sufficient to get rid of the cancer. If the tumour is classed as high risk, chemotherapy and possibly radiotherapy will also be needed. If the tumour is too large, or in too difficult a position to remove safely, chemotherapy will be given to shrink it before surgery.

If the tumour has spread to several parts of the body or is high-risk with MYCN amplification, high-dose chemotherapy is used to eradicate any remaining neuroblastoma cells. High-dose chemotherapy also destroys the child’s bone marrow, however, so stem cell rescue will be required. This involves collecting blood stem cells from the child before chemotherapy and returning them afterwards, via a drip. The stem cells make their way back into the bone marrow where they grow and develop into mature blood cells over a period of several weeks.

Radiotherapy may be used if the neuroblastoma is classed as high-risk or if it has spread to several parts of the body. This may be either external radiotherapy, delivered from a machine outside the body, or internal radiotherapy using radioactive mIBG.

Children under 18 months old generally have a good outlook. Most neuroblastomas in this age group are stage 4S and regress spontaneously, without treatment. Treatment will only be given if the tumour is causing life-threatening symptoms or if it has spread to the bone, lungs or central nervous system.

A new type of immunotherapy called anti-GD2 therapy is currently being tested for children with high-risk neuroblastoma. Results indicate that this may be a promising therapy when given alongside other standard treatment for neuroblastoma; however it has unpleasant side-effects and is still undergoing trial. In the UK it is currently only available to certain children who are being treated within a clinical trial.

Side effects and complications of the treatment

The possible side effects depend on the treatment given and the part of the body being treated but may include nausea and vomiting, hair loss, reduced resistance to infection, bruising and bleeding, tiredness and diarrhoea. 

These problems are all temporary and can be minimised with good supportive care.

A small number of children may develop late effects because of the treatment they received for neuroblastoma. These include possible problems with heart and kidney function, hearing problems, fertility problems, a possible reduction in bone growth if radiotherapy has been used, and a small increase in risk of developing another cancer.

Follow-up

Children will have regular follow-ups to check for any recurrence of the cancer and for any late effects of treatment.

If the cancer comes back after treatment it is called relapse. The risk of relapse can be linked to certain risk factors.

Generally, the outlook is likely to be better if:

• The child is younger
• The cells are more normally developed and so the cancer is likely to grow more slowly (this is called ‘low grade’)
• The neuroblastoma cells do not have a particular abnormal gene called MYCN

Many children have their treatment as part of a clinical trial.

Trials aim to improve our understanding of the best way to treat the cancer, usually by comparing the standard treatment with a new or modified version.

If appropriate, the child’s medical team will discuss participation in a relevant trial. Participation is optional but may offer the opportunity to receive new treatments.

Children with Cancer UK is funding a number of research projects focused on neuroblastoma.

Read about Emma’s victory against neuroblastoma, as told by her mum, Samantha.

Emma developed a cough; the doctors said it was normal as she had started teething. The cough never seemed to go away but the doctors said it was a just a cold or a viral infection. On 12 November 2006, we took Emma back into hospital because she was still in pain. We saw a different doctor in A&E and he found a lump in Emma’s belly. Our lives changed forever. Emma was diagnosed with stage 4 high risk neuroblastoma on 27th November 2006. She was just two years old at the time. That evening the doctor told us she only had a 20% chance of surviving. We used this as a positive – we had a chance!

Emma did her nine months of maintenance chemotherapy and was told not every child can finish this part of treatment as it cracks the skin, dries it out and it almost looks like they have been burnt. Yet again Emma was amazing, she took all 22 tablets a day.

Emma responded well to all the chemotherapy she was given and the tumour shrunk by more than half its size in just four rounds; her bones and bone marrow were all clear, which was amazing.

Emma is nine years cancer free. I can’t believe how quickly it has gone. These last nine years have been truly amazing, watching Emma grow into a lovely young girl.

If you’ve been touched by Emma’s journey, help us invest in the high quality research that really matters which would otherwise go unfunded. This helps to support children with cancer so they can be with their families for longer.

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