This page is about neuroblastoma. There is information about
- What neuroblastoma is
- Causes of neuroblastoma
- Neuroblastoma symptoms
- Referral to a specialist
- Tests to diagnose neuroblastoma
- Neuroblastoma stages and risk groups
Neuroblastoma is a rare cancer that affects children, mostly under the age of 5 years old. Around 100 children are diagnosed with neuroblastoma each year in the UK. Very rarely it can occur in older children, teenagers and adults.
Neuroblastoma develops from particular types of nerve cells called neuroblasts.
- ‘Neuro’ means nerve
- ‘Blast’ means cells in early development
- ‘Oma’ means a group of cells, or a tumour
Neuroblastoma often starts in the tummy (abdomen), commonly in the adrenal glands or the nerve tissue at the back of the abdomen.
Like other cancers it can spread to other parts of the body. The most common places are the bones, liver and skin. It spreads through the blood and lymphatic system. This happens in about half of children with neuroblastoma.
Neuroblastomas often produce substances called catecholamines (cat-a-coal-ay-meens) for example adrenaline. The adrenal glands make catecholamines. They are chemical messengers that send messages between nerve cells. Our bodies break them down into substances that we pass out in urine. Neuroblastoma tumours often produce catecholamines in large amounts. Tests can measure the amount of this substance in blood as well as the substances which are found in urine.
We don’t know exactly what causes neuroblastoma. In some cases there is a family history of neuroblastoma. But these cases are very rare (1 in every 100 diagnosed).
Neuroblastoma usually develops in the abdomen and when it does the most common symptom is a lump in the tummy. This may make the child’s tummy swell, causing discomfort or pain.
Occasionally, it can affect the spinal cord. This can cause numbness, weakness and loss of movement in the lower part of the body. And rarely it can appear as a lump in the neck, perhaps causing breathlessness or difficulty in swallowing.
Other symptoms depend on where the neuroblastoma starts in the body and whether it is just in one place (localised) or has spread to other parts of the body.
Symptoms when neuroblastoma has spread
In around half of children the neuroblastoma has spread to another part of the body at diagnosis. The symptoms depend on where it has spread to but are often vague such as tiredness, fever and loss of appetite.
This the most common place for neuroblastoma to spread to. Symptoms include pain, sometimes with swelling over the bone and difficulty in walking. Occasionally it can affect the spine causing numbness, weakness and loss of movement in the lower part of the body.
Spread to the bone marrow may cause
- Tiredness and paleness due to a low red blood cell count (anaemia)
- Bruising or bleeding due to a low platelet count (sometimes around the eyes)
- Infections due to a low white blood cell count
If neuroblastoma spreads to the skin it can give it a blue black colour, as if it were bruised.
This may cause tummy pain and babies may have difficulty feeding because the liver has got bigger .
Most children with neuroblastoma have higher than normal levels of catecholamines. The doctor will test for this, it is very unusual for it to cause any symptoms. But very large amounts of catecholamines and other chemicals the cancer produces can cause symptoms such as
- Weight loss
- Redness of the skin (flushing) or paleness
- A fast heart beat and increased blood pressure
- Watery diarrhoea
Your GP should refer you to a specialist within 2 days if you have a lump in the tummy (abdomen), or if you have an enlarged or swollen organ in your tummy.
Doctors carry out a number of tests if they suspect neuroblastoma. These aren’t generally painful. But your child will have to keep still for some of them. They are likely to need sedation or a general anaesthetic for some tests. Tests may include
- Blood tests
- A chest X-ray
- CT scan
- An MRI scan
- A bone scan
- A biopsy this means taking a sample of tumour cells to examine in the lab
- A bone marrow biopsy this is a sample of cells from the bone marrow to see if there are neuroblastoma cells
Doctors can use urine tests to help diagnose neuroblastoma. The waste products from catecholamines made by neuroblastoma cells are passed out of the body in the urine. Doctors can then test for these for chemicals, called HMA (homovanillic acid) and VMA (vanillylmandelic acid).
MIBG is a particular type of scan used to diagnose neuroblastoma. Neuroblastoma cells absorb a substance called MIBG. Doctors attach a very small amount of radioactive iodine to MIBG and then inject this into the bloodstream. The neuroblastoma cells pick up the MIBG and then the radioactive iodine attached to it shows up on the scan.
The stage of a cancer describes how far it has grown or spread. Doctors use the stage as well as the child’s age and results of other tests to make a decision about treatment.
There are a number of different staging systems. The newest system uses imaging tests such as CT scans, to look for particular risk factors. These factors are a sign that it is more difficult to treat, for example they will look at whether the tumour is wrapped around an organ. These risk factors are called Image Defined Risk Factors.
The staging system doctor’s use most often is shown first and the newer staging system is in brackets.
Stage 1 and 2 (L1)
The tumour is in one area of the body and hasn’t spread anywhere
Stage 3 (L2)
The tumour has spread into nearby structures but not far. Tests show some image defined risk factors
Stage 4 (M)
The cancer has spread to parts of the body that are some distance from where it started
Stage 4S (MS)
This a special case, as these children have a better outlook than other stage 4 patients. Stage 4S means the child is younger than 18 months at diagnosis. The neuroblastoma may have spread to the liver or skin, but not to the bones. And less than 10% of the cells in the bone marrow are neuroblastoma cells.
As well as staging the neuroblastoma doctors also group children into risk groups, according to their risk of the cancer coming back. There are 3 risk groups based on these factors – low, intermediate and high risk.
Doctors take into account a number of different things including
Children younger than 18 months are at lower risk.
What the tumour looks like under a microscope (histology)
Tumours with more normal looking cells tend to be lower risk.
A gene called MYCN controls cell growth. Some neuroblastoma tumours have too many of these genes. This means that the cells grow quickly and are less likely to mature. Tumours with too many MYCN genes tend to be higher risk.
Another gene change doctors look for is how much DNA there is in the cells. Genes are made of DNA and they are grouped together to make chromosomes. Changes in these and how much DNA there is in a cell can affect how well treatment works.
Treatment depends on
- The stage, and
- The risk group, whether there is a low, medium or high risk of the cancer coming back after treatment
Babies with low-risk neuroblastoma such as those who have no high risk changes and no symptoms may not need much treatment, or any treatment at all. This is stage MS or 4S. This kind of neuroblastoma can sometimes disappear on its own. Doctors always keep a close eye on children who have had neuroblastoma, so they will have hospital appointments for some years.
Children with all other stages of neuroblastoma need to have treatment. They may have surgery, chemotherapy or radiotherapy or a combination of all of them. The treatment they need depends on which risk group they are in.
Low risk neuroblastoma (stage L1)
Treatment for low risk neuroblastoma is usually either surgery alone or chemotherapy and surgery.
Intermediate risk neuroblastoma (stage L2)
Children with intermediate risk neuroblastoma usually need chemotherapy and surgery and may need radiotherapy.
High risk neuroblastoma (stage M)
Treatment for high risk disease has 4 parts
The first treatment children with high risk disease have is chemotherapy. This is to either get rid of or reduce the cancer that has spread.
Local control treatment
The second part of treatment is an operation to remove the main tumour. This is followed by radiotherapy to where the tumour was. The aim is to kill any remaining cells and reduce the likelihood of the cancer coming back
This is the third treatment. It is high dose chemotherapy with a stem cell transplant.
After consolidation treatment there is still a small chance the cancer could come back. This is due to neuroblastoma cells that haven’t been killed by the other treatments. Doctors call this minimal residual disease or MRD. If they are left they could develop into another tumour. Research has shown that having maintenance treatment can help reduce the chance of this happening.
Maintenance treatment involves having two types of treatment. A substance related to vitamin A, called 13-cis-retinoic acid (isotretinoin). Your child takes this as a capsule for about 6 months. Taking it twice a day for 2 weeks and then having 2 weeks off then starting again. Side effects included skin changes including dry, cracked lips, dry eyes, nosebleeds and muscle and joint pain.
The other treatment helps the immune system to find and kill any mature neuroblastoma cells. It is a type of immunotherapy called monoclonal antibody treatment.
Monoclonal antibody treatments are manmade versions of proteins the immune system produces. They can be made to recognise and attach to specific proteins on neuroblastoma cells. This can help the immune system recognise the neuroblastoma cell and kill it. The treatment is called anti GD2.
Your child will have immunotherapy by injection into the blood system, usually through their central line. The treatment usually lasts for about 16 weeks or 4 months.
The main side effects are pain, low blood pressure and a fast heart beat. This happens because of movement of fluid in the body and an allergic reaction. The nurses will keep a close eye on them while they are having treatment.
To help the immune system work your child may also have injections of blood cell growth factors to produce more cells to attack the neuroblastoma cells.
Researchers are still looking into what the best maintenance treatment is. So, your child’s doctor may ask you if your child will take part in a trial to look into different treatments.
Treatments for neuroblastoma include
The surgeon will try to remove the whole tumour, or as much of it as possible. The exact type of surgery depends on where the tumour is in the body. If the tumour hasn’t spread, and it’s possible to remove it all, surgery may be the only treatment your child needs.
Your child will need to stay in hospital. How long will depend on the surgery they have.
This uses drugs to kill cancer cells. Doctors usually give a combination of chemotherapy drugs, usually 2 or 3 different ones.
The most common side effects of chemotherapy are
- Hair loss
- Feeling sick
- An increased risk of infection
- A sore mouth
Your child will have a central line put in while they are having treatment. This is a tube that is put into one of the large veins in the chest. They have their chemotherapy through it and can have blood taken from it. It means that they need fewer needles. They keep it in throughout their treatment.
There are different types of central lines. Find out more about central lines.
Some children need more intensive or high dose chemotherapy. High doses of chemotherapy can damage the bone marrow and kill off the cells that make blood cells. These cells are called stem cells. So, as part of this high dose treatment they need to have treatment to replace these blood stem cells.
This means early on in the treatment the doctors collect some blood stem cells and store them until after they have had the high dose chemotherapy. Then after the high dose treatment they have the stem cells back. This is called a stem cell transplant.
This is the use of high energy X-rays to kill cancer cells. This is usually external beam radiotherapy. This means radiotherapy aimed at the cancer from outside the body. Your child is most likely to have this after surgery to reduce the risk of the cancer coming back.
If your child’s neuroblastoma is advanced and chemotherapy is not working they may need targeted radiotherapy. Or, they may need it if their neuroblastoma has come back after earlier treatment.
Targeted radiotherapy is similar to the MIBG scan used to diagnose neuroblastoma, but gives a higher dose of radioactive iodine. The MIBG is picked up by the cancer cells.
The dose of radioactive iodine attached to the MIBG is high enough to kill the neuroblastoma cells, but not to cause serious side effects to surrounding tissues. But this treatment can damage the bone marrow and kill off the cells that make blood cells. So, children having this treatment also need a stem cell transplant.
Immunotherapy is a type of drug treatment to help the immune system kill cancer cells. It is a type of biological therapy. Your child is likely to have this if there is a high risk of their neuroblastoma coming back.
You can read more general information about these treatments
Neuroblastoma that comes back after treatment is called recurrent disease. The treatment your child needs depends on a number of factors including where it has come back and the original risk group they were in.
If your child has low or intermediate risk disease that has come back where it started they may need surgery again with or without chemotherapy.
If they have high risk disease treatment is usually more intense and is likely to include a combination of treatments again. The chemotherapy is likely to be different drugs from their first treatment.
Or they may need targeted radiotherapy. Targeted radiotherapy is similar to the MIBG scan used to diagnose neuroblastoma, but gives a higher dose of radioactive iodine. The MIBG is picked up by the cancer cells.
It can be more difficult to treat cancers that come back after the first treatment and your doctor may suggest your child has treatment as part of a clinical trial. This is likely to be trying newer treatments.
Doctors are always looking to improve the diagnosis and treatment of neuroblastoma. Many children and young people with neuroblastoma will have their treatment as part of a clinical trial.
To find out about UK trials into neuroblastoma talk to your child's specialist or look on our searchable clinical trials database. Type 'neuroblastoma' into the search box.
Research looking into diagnosing neuroblastoma
Researchers are looking into different types of scans to see which is better at showing where neuroblastoma has spread in the body.
Research into treatment
Doctors are looking into improving the treatment for high risk neuroblastoma. A European trial is comparing different chemotherapy drugs as the first treatment children have.
Doctors are looking at new immunotherapies including monoclonal antibodies (MAB) and different ways of giving them.
MABs can cause pain and children often need strong painkillers when they have them. One trial is looking at giving a MAB called ch14.18/CHO slower over a number of days. The aim is to see if giving it this way means that children need less strong painkillers and don’t need to stay in hospital. This is for children having it as maintenance treatment.
Another trial called BEACON – neuroblastoma is looking into whether having a MAB called bevacizumab with chemotherapy works better than chemotherapy alone. This trial is also comparing different combinations of chemotherapy to see which works best. The trial is for children whose chemotherapy is no longer working and for those who have finished treatment and their neuroblastoma has come back.
Other research is looking at new ways of delivering radiotherapy directly to the cancer cells. Many neuroblastomas have a particular protein on their cells called somatostatin. Researchers think they can use these proteins to deliver a dose of radiotherapy to the neuroblastoma.
Drugs called somatostatin analogues can target somatostatin on the surface of neuroblastoma cells. LuDO is a somatostatin analogue that has a radioactive molecule attached to it. LuDO finds the neuroblastoma cells and then the radioactivity kills them.
A study in 2014 showed that particular markers found in the blood at diagnosis can help show which children with stage 4 neuroblastoma have high risk disease that may not respond as well to standard treatment. Knowing this early on may help doctors decide to give newer treatments straight away for this group of children instead of standard treatments. We need more research to see how helpful these blood tests are.
Researchers are looking at collecting tumour cells that have broken away from neuroblastoma and are circulating in the blood (circulating tumour cells). They want to find out if it's possible to collect these cells from the blood and bone marrow. And if so, use these cells to help develop new drugs to treat neuroblastoma.
Research into side effects of treatment
Researchers are also looking into the long term effects of treatment for all types of childhood cancer. The Centre for Childhood Survivor Studies is carrying out the British Childhood Cancer Survivor study. This research is looking at children who were diagnosed with cancer between 1940 and 1991 and lived for at least 5 years after diagnosis.
This type of research takes many years to produce results because the children need to be followed throughout their lives. So it will be some time before we know the results.
Many parents worry about the possible long term effects of treatment. Some children treated for neuroblastoma go on to develop long term side effects. But not everyone has them. The possible long term effects depend on
- The type of treatment the child has had
- The treatment doses they had
- The age they were when they had treatment
It is important to remember that the risk needs to be weighed up against the benefits of treatment. For many children, treatment will cure their cancer.
The risk of long term effects is also becoming less as treatments improve.
Possible long term effects include
- Fertility problems
- Hearing problems
- Changes in how the kidneys and heart work
- Growth problems
- Risk of developing a second cancer
Your child’s doctor will talk to you about the possible risks depending on the treatment your child has had. They will continue to keep a close eye on your child, so that any problems can be treated early. They will work out the best way to follow them up depending on the treatment they have had. Children who have had cancer should have follow up into adult hood. They will eventually be followed up by a late effects team which includes different types of health care professionals.
When your child finishes treatment their doctor will provide you with a summary. This includes information about what type of cancer they have had, details of their treatment, the risk of late effects and what follow up they should have.
The National Cancer Survivorship Initiative is looking into the best way for children and young people to be followed up. The Scottish Intercollegiate Guidelines Network (SIGN) have produced guidelines about how children should be monitored after childhood cancer. These include recommendations about which professionals should be involved in following the child into their adult life.
It is extremely distressing to find out that your child has cancer. It can raise many different emotions. You will probably feel angry, sad, upset and shocked. This is very normal. It is such a lot to take in. You are likely to worry about whether they will get the right treatment, what will happen, and how you will all cope.
If you have other children most parents and grandparents worry about them as well. Practical help and support is something people nearly always need, for example, shopping or help with looking after other children in the family.
It is essential that parents and other close family also have support. Talking to friends and other members of the family can help you deal with your feelings. We have information about emotions and cancer.
Sources of help
Cancer Research UK
General organisations information some organisations can put you in touch with a cancer support group. Our cancer and treatments reading list has information about books, leaflets and other resources about cancer treatment.
Cancer Research UK information nurses will be happy to answer any questions that you have. You can call them on freephone 0808 800 4040. The lines are open from 9am to 5pm, Monday to Friday.
Cancer Chat forum is a place to share experiences online with other people
The Neuroblastoma Society is run by the parents and grandparents of children with neuroblastoma. They have a befriending scheme for affected families.
The Children's Cancer and Leukaemia Group (CCLG) - produce booklets for parents and brothers and sisters of children with cancer that you may find helpful. You can download these from their website.You can phone the Cancer Research UK nurses on freephone 0808 800 4040. The lines are open from 9am to 5pm, Monday to Friday. They will be happy to answer any questions that you have.
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