Neuroblastoma in children

Neuroblastoma develops from the cells left behind from a baby’s development in the womb. The cells that it develops from are called neuroblasts.

‘Neuro’ means nerve
‘Blast’ means cells in early development
‘Oma’ means a group of cells, or a tumour

Neuroblastoma starts from either the adrenal glands (situated in the tummy) or from nerve tissue that runs alongside the spinal cord in the neck, chest, abdomen (tummy) or pelvis. The adrenal glands are found above the kidneys. They release hormones to maintain blood pressure, and enable us to respond to stress.

Watch Dr Boo Messahel, Consultant Paediatric Oncologist and CCLG member, explain more about neuroblastoma.

Causes

The exact cause of neuroblastoma is not known. It is not infectious and cannot be passed on to other people.

It is important to remember that nothing you have done has caused your child’s cancer.

Signs and symptoms

The symptoms vary, depending on where your child’s neuroblastoma tumour is. Symptoms may include:

swollen tummy
constipation
difficulty weeing
breathlessness or difficulty swallowing
visible lump
small, blue-coloured lumps in the skin
leg weakness or unsteadiness
reduced leg movements
jerky eye and muscle movements
non-specific symptoms of tiredness, pallor, loss of appetite, weight loss, bone pain and general discomfort.

How is neuroblastoma diagnosed?

A variety of tests and investigations are needed to diagnose neuroblastoma. These include a biopsy, blood and bone marrow tests, x-rays, CT or MRI scans, and a special nuclear medicine scan called an MIBG scan (see below). These tests will help to confirm the diagnosis to find the original site of the tumour and to see whether it has spread. Any tests and investigations that your child needs will be explained to you.

Urine test

Nine out of ten children with neuroblastoma will have the substances, vanillylmandelic acid (VMA), or homovanillic acid (HVA), in their urine. These are sometimes called ‘tumour markers’. Measuring VMA and HVA can help to confirm the diagnosis. VMA and HVA levels will be checked during and after treatment.

MIBG (nuclear medicine) scan

Most children will have an MIBG (meta-iodo-benzyl guanidine) scan. Attaching a small amount of radioactive iodine to the MIBG makes neuroblastoma tissue show up on the scanner. Some children have neuroblastoma that does not take up MIBG and a FDG-PET scan may be needed instead.

Biopsy

A small sample of cells is taken from the tumour during an operation under a general anaesthetic. The biology and genetics of these cells are looked at. The presence of a certain amount of a ‘marker’ called MYCN (known as MYCN amplification) can suggest that the neuroblastoma may be an aggressive type. In this situation, the treatment needs to be 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 the doctors to decide on the most appropriate treatment for your child.

The staging system below is commonly used:

Stage 1 (INRG stage L1) – the tumour is in one place, and can be removed completely by an operation.
Stage 2 (INRG stage L1) – .the tumour is in one area and has not spread. It may be larger than stage 1 and more difficult to remove completely by an operation.
Stage 3 (INRG stage L2) – the tumour has not spread but it may be large and have grown from one side of the child’s body to the other. This type of tumour is usually difficult to safely remove with surgery alone.
Stage 4 (INRG stage M) – the tumour may be any size, but some neuroblastoma cells have broken away and spread to other parts of the body. Depending on age, children with stage 4 neuroblastoma are likely to need more intensive treatment.
Stage 4s (INRG stage MS) – most often found in babies, under one year old. The tumour cells may have spread, but often behave less aggressively than in an older child. As well as a primary tumour, the liver, skin, lymph nodes and sometimes bone marrow may be affected but not bones, lungs or brain.

Treatment

The treatment of neuroblastoma depends on the age of your child, the size and position of the tumour, risk factors shown on scan images, the tumour biology (including the MYCN status) and whether the cancer has spread. Based on these features your child’s neuroblastoma will be classified as very low, low, intermediate, or high-risk disease and treatment will be planned accordingly.

Information videos

A series of videos have been made for young patients and their families to explain the different stages of treatment for high-risk neuroblastoma, along with information about the high-risk neuroblastoma 2 study (HR-NBL2). We hope you find these helpful. These videos were developed by CCLG in partnership with Solving Kids Cancer National Neuroblastoma Nursing Group including input from parents and families.

Surgery

If the tumour is at an early stage and there is no evidence that it has spread to the lymph nodes or any other parts of the body, an operation to remove it, or as much of it as possible, will be undertaken. If the tumour is, too large or in too difficult a position to remove safely, 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 drugs to destroy cancer cells. It is usually given as an infusion into a vein. Your child will have a semi-permanent cannula called a central venous line inserted under a general anaesthetic to minimise the distress caused by intravenous injections.

Your child’s specialist will discuss with you the type and amount of chemotherapy needed.

High-dose chemotherapy with stem cell rescue

If your child has high-risk neuroblastoma, they are likely to have high dose chemotherapy with peripheral blood stem cell rescue. High-dose chemotherapy wipes out any remaining neuroblastoma cells but also wipes out the body’s bone marrow, where blood cells are made. To prevent the problems this causes, stem cells (blood cells at their earliest stages of development) are collected from your child’s blood before the chemotherapy is given. These stem cells are frozen and stored until required. After the high-dose chemotherapy, the stem cells are given back to your child through their central line. They make their way into the bone marrow, where they grow and develop into mature blood cells.

Radiotherapy

External beam 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 beam 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 MIBG scan to diagnose a neuroblastoma, but uses higher doses of radioactivity to kill the cancer cells.

Immunotherapy

Immunotherapy (monocolonal antibodies) can encourage a patient’s immune system to destroy some types of cancer cells while causing little harm to normal cells. Children with high-risk neuroblastoma, are usually given immunotherapy using an antibody called anti-GD2 (dinutuximab-beta). Evidence shows that anti-GD2 monoclonal antibodies can reduce the risk of relapse or delay the timing of relapse. Each course of dinutuximab beta is given over 10 days and some children can be at home for parts of each course. The treatment has side effects, which your doctor will discuss in detail.

Dinutuximab-beta is combined with a medicine taken by mouth called retinoic acid, which is similar to vitamin A. This medicine helps to stop cancer cells growing and helps them to transform into non-cancerous cells.

Continuation therapy with DFMO

Following approval by the Food and Drug Administration (FDA) in the US in December 2023 of the use of eflornithine (difluoromethylornithine or DFMO), guidelines for treatment of neuroblastoma in the US were updated, with a recommendation that doctors discuss DFMO as a continuation therapy option with patients and families, and it is now being widely prescribed in the US. The UK Neuroblastoma Clinical Trials Group and CCLG Neuroblastoma Special Interest group suggest that treatment with DFMO for high-risk neuroblastoma patients, is considered and discussed with patients and families who are completing frontline therapy or relapse therapy. For further information, please see our patient information sheet below.
Eflornithine (DFMO) in the treatment of high-risk neuroblastoma patients: Information for patients and families
This section added 08.10.24: review date 07.10.27

Younger children

Children under 18 months old with neuroblastoma often have ‘low-risk’ tumours, and as long as there is no MYCN amplification, their outlook is excellent.

Children with Stage 4S disease often get better with very little treatment or none at all. These tumours can regress spontaneously or after chemotherapy, which is only given if the tumour is causing symptoms. They disappear completely or develop into a non-cancerous (benign) tumour, called a ganglioneuroma. Ganglioneuromas are usually harmless and do not need any treatment.

Clinical trials

Many children have their treatment as part of a clinical research trial or study. Trials and studies are carried out to try to improve our understanding of the best way to treat an illness. There are better results for curing children’s cancers compared with just a few years ago because of clinical trials. The European research group for neuroblastoma is called SIOPEN (www.siopen.net).

Your child’s medical team will talk to you about taking part in a clinical trial, and will answer any questions you have. Taking part is completely voluntary, and you’ll be given plenty of time to decide if it’s right for your child. You may decide not to take part, or you can withdraw from a trial at any stage. Your child will still receive the best treatment available.

National treatment guidelines

Sometimes, clinical trials are not available for your child’s tumour. In this case, your doctors will offer the most appropriate treatment, using guidelines which have been agreed by experts across the UK. Children’s Cancer and Leukaemia Group (CCLG) is an important organisation which helps to produce these guidelines.

Useful links

Solving Kids Cancer is a neuroblastoma-focused charity that provides family support services for families of children affected by neuroblastoma; provides evidence-based and impartial information to help families choose treatment options for their child and to access treatments and clinical trials if they are not available on the NHS; funds research and campaigns on important issues for families affected by neuroblastoma.Solving Kids Cancer

Neuroblastoma UK funds research into improving both diagnosis and treatment of neuroblastoma.
Neuroblastoma UK

SIOPEN is the international organisation bringing together healthcare professionals from across Europe and beyond to improve treatments for children with neuroblastoma.
SIOPEN

Reviewed by

Professor Deb Tweddle
Professor of Paediatric Oncology, Great North Children’s Hospital, Newcastle
Dr Martin Elliot
Consultant Paediatric Oncologist, Leeds Children’s Hospital
Content last reviewed: February 2023
Next planned review: February 2026