Neuroblastomas are neuroendocrine tumours that develop from neuroblast cells (young nerve cells) in nerve tissue. Neuroblasts are most commonly found in the adrenal glands, which are located on top of the kidneys; however, they can also be found in the nerve tissues of the neck, chest, abdomen or pelvis. 

Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreas and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response. 

Neuroblastomas are the most common type of solid childhood tumour and is usually diagnosed between birth and five years of age. However, it can be diagnosed in people at any age.

Treatment 

If a neuroblastoma is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system:

• T (tumour) indicates the size and depth of the tumour.
• N (nodes) indicates whether the cancer has spread to nearby lymph nodes.
• M (metastasis) indicates whether the cancer has spread to other parts of the body.

This system can also be used in combination with a numerical value, from stage 0-IV:

• Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
• Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
• Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
• Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
• Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.
  

Cancers can also be graded based on the rate of growth and how likely they are to spread:

• Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
• Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour. 
• Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour. 

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you. 

Treatment is dependent on several factors, including location, stage of disease and overall health.

Surgery

Surgery is most often used in patients who have a tumour that hasn’t metastasised (spread to other parts of the body). The procedure itself will vary depending on the location and size of the tumour, but usually involves removing the tumour and a margin of healthy tissue to prevent recurrence. Your surgeon will discuss the most appropriate surgery for you, risks and any potential complications with you prior to the commencement of treatment.
In many cases, surgery is used in conjunction with chemotherapy and radiation therapy due to the unpredictable nature of this disease.

Radiation therapy

Radiation therapy, or radiotherapy, uses controlled doses of radiation to damage or kill cancer cells. It can be administered internally or externally. This may be a satisfactory alternative if you are not a suitable candidate for surgery, or, may be used in conjunction with surgery. This treatment option is most often used to treat EHE that grows in the bones.

Chemotherapy

Chemotherapy uses drugs to kill or slow the growth of cancerous cells, while minimising the damage to healthy cells. It is usually administered directly to the veins (intravenously), however in some cases in can be administered orally. You may receive a single chemotherapy drug, or a combination, depending on your individual factors. It is usually done in cycles of treatment sessions and periods of rest and can last several months. This treatment option can be used on its own, or in addition to other treatment options. This treatment is more commonly used in patients whose cancer has metastasised.

Immunotherapies

Immunotherapy is a treatment option that aims to enhance the immune system to fight cancer cells. The immune system is a network of cells, tissues, chemicals and organs that recognises abnormal cells in the body and then attacks them so it doesn’t harm the body. This process is also known as an immune response. Cancer cells are able to prevent an immune response, usually by either setting up barriers so immune cells can’t recognise them, or by constantly mutating to avoid being detected. 

There are four primary types of immunotherapies that may be used to help the immune system provide an immune response:

• Checkpoint inhibitors, which are the most common type of immunotherapy. These drugs work to inhibit the growth of the cancer cell barriers.
• Immune stimulants, which help to stimulate and reactivate the immune system to fight the cancer cells.
• CAR T-cell therapy (chimeric antigen receptor T-cell therapy), which boosts the ability of white blood cells (specifically T-cells) to fight cancer cells.
• Oncolytic virus therapy, which uses genetically altered viruses to target and attack cancer cells.

Ask your doctors about the availability of immunotherapies and whether you are suitable, as well as any benefits, risks and potential complications that may arise.  

Clinical trials  

Clinical trials are research studies performed to test new treatments. They present the opportunity for people, particularly those with rare or complex cancers, to receive very new treatments which are not yet available otherwise. While these studies have the potential to develop more treatment options, the risk of side effects can be high and are not always known. These trials might involve targeted therapies (to target only the cancer cells), hormonal therapies or immunotherapies.

Clinical trials are often conducted in phases:

• Phase 0: these trials are used to determine how the body will react to experimental drugs. They are given in very small doses to very few people.
• Phase I: these trials are used in slightly bigger groups (20-80 people) to determine the safety of the drug, as well as any potential side effects that may arise.
• Phase II: these trials are used in larger groups (several hundred people) to further evaluate the safety of the drug, as well as whether it is working as it should be.
• Phase III: these trials are used in groups of several hundred to several thousand people. They are used to monitor any adverse effects of the drug, as well as compare it to other conventional or experimental treatment methods.
• Phase IV: these studies test the drug in the general population to determine any long-term adverse effects, as well as potential usage in treatment of other conditions. 

Vaccine therapies

Researchers are currently studying the use of cancer vaccines as potential treatment options. Much like vaccines that fight viruses, cancer vaccines are made to target specific antigens on specific cancer cells, which would then trigger an immune response. They can be made from proteins, DNA and/or RNA, whole cells, dendritic cells or genetically altered viruses. However, more research is needed to understand how effective these treatments are and any potential long- and short-term side-effects that may arise.

Ask your doctors about the availability of clinical trials and whether you are suitable, as well as any benefits, risks and potential complications that may arise. 

Palliative care

Palliative care aims to improve the patient’s quality of life and alleviate symptoms, without trying to cure the disease. This option is beneficial for patients with an advanced neuroblastoma at any stage of treatment, not just towards the end of life. It may also be used in conjunction with other treatment options, such as surgery, radiotherapy and chemotherapy, with the intention of relieving pain, alleviating symptoms and meeting your physical, emotional, cultural and spiritual needs.

Risk factors

While the exact cause of neuroblastomas remains unknown, the following factors have been linked to a higher chance of developing the disease:

• Family history of Neuroblastoma.
• Certain genetic conditions, such as Hirschsprung disease, congenital central hypoventilation syndrome (CCHS) and neurofibromatosis type 1 (NF1).

Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.

Early symptoms

The symptoms of neuroblastomas will vary depending on stage, location and whether the tumour has metastasised (spread to other parts of the body). Some of these symptoms include:

• Lump or swelling in the affected area.
• Abdominal pain.
• Unexplained weight loss/loss of appetite. 
• Issues urinating and/or with bowel movements.
• Exophthalmos (bulging eyes).
• Dark circles around the eyes. 
• Uncontrolled eye movements.
• Bone and/or other unexplained pain.
• General weakness or paralysis.
• Difficulties breathing and/or swallowing.

In some cases, neuroblastomas release hormones that causes additional symptoms:

• Diarrhoea.
• High blood pressure.
• Rapid heartbeat.
• Unexplainable sweating.
• Flushing of the skin.

Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.

Diagnosis/diagnosing

If your doctor suspects you have a neuroblastoma, they will order a range of diagnostic tests. 

Imaging & blood tests 

The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-ray, bone scan, metaiodobenzylguanidine (MIBG) scan and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis. Additionally, a blood and urine test may also be taken to assess your overall health and help guide treatment decisions. 

Biopsy 

Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. In most cases, this will be done by a bone marrow aspiration and biopsy. This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for cancer cells. 

Prognosis (Certain factors affect the prognosis and treatment options)

While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on stage, rate/depth of tumour growth, susceptibility to treatment, age, overall fitness and medical history. Generally, early-stage neuroblastomas have good prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence.  

References

• Cancer Australia
• Neuroendocrine Cancer Australia

^{Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.}