Neuroendocrine tumours

A neuroendocrine tumour (NET) is a tumour that grows from cells of the neuroendocrine system.

Neuroendocrine cells are similar to nerve cells. They make chemical messengers called hormones, and these hormones control how different organs in the body work.

You'll find neuroendocrine cells all over the body, for example in organs like the stomach, bowel, pancreas and lungs.

Tumours that grow from neuroendocrine cells are known as neuroendocrine neoplasms (NENs). Most NENs are neuroendocrine tumours (NETs). A smaller number are called neuroendocrine carcinomas (NECs).

Whether a tumour is called a NET or a NEC depends on its grade. A doctor decides the grade of the cancer by looking at the cancer cells under the microscope. This gives an idea of how quickly the cancer might grow or spread.

NETs can be non-cancerous (benign) or cancerous (malignant). This information is about malignant NETs, and mainly about those that affect the digestive system.

Some neuroendocrine tumours (NETs) make extra hormones and cause symptoms. These are called functioning tumours. Tumours that don't make extra hormones are called non-functioning tumours.

Doctors group NETs according to where the cancer started (the primary tumour). For example:

• small bowel NETs
• large bowel NETs
• rectal NETs
• appendix NETs
• pancreatic NETs
• stomach (gastric) NETs
• lung NETs

NETs can also occur in other areas, including the:

• liver
• gallbladder
• bile ducts
• kidneys
• ovaries
• testicles

You may hear some NETs called carcinoid tumours. These are usually found in the bowel or the lungs.

NETs often grow slowly. They can be difficult to diagnose, because they may not cause symptoms for several years. But some NETs grow faster and are more likely to spread to surrounding tissues and parts of the body.

Macmillan Cancer Support have more information on what cancer is.

Doctors don't know what causes neuroendocrine tumours (NETs). They can affect people of any age, children included, but most are diagnosed when a person is around 50 or 60 years old.

Around 1 in 20 (5%) of NETs occur in people who have a hereditary (genetic) condition. One rare genetic condition, multiple endocrine neoplasia 1 (MEN1), raises the risk of developing NETs.

Other rare genetic conditions can also raise the risk of NETs:

• von Hippel-Lindau (VHL) disease
• tubular sclerosis (TSC)
• neurofibromatosis (NF)

People with these hereditary conditions may develop NETs at a younger age. So if you're diagnosed with a NET when you're young, you may be offered genetic testing.

You may also be offered testing if NETs run in your family, or if you have other symptoms that could be caused by one of these hereditary conditions.

Diagnosis of a neuroendocrine tumour (NET) usually starts with a visit to your doctor. If they're unsure of the problem, they'll refer you to a specialist at the hospital.

At the hospital, the doctor will ask about your general health and any previous medical problems. They'll then examine you and talk with you about the tests you need to have. Sometimes a NET shows up on a scan you're having for another reason.

You may have some of the following tests.

If you have a NET, the levels of some chemicals in your blood may rise. This is mainly:

• serotonin
• 5HIAA
• a protein called chromogranin A (CgA)

Serotonin is a natural chemical made by the body. It sends messages between different parts of the brain. It helps control lots of functions, like how you sleep, your mood and your appetite.

You'll need to give blood samples to check the levels of these chemicals. You may be asked to fast (not eat) before these tests. You may also have a blood test to look for hormones released by some NETs.

You'll also have general blood tests to count the number of healthy blood cells in your blood. This is called a full blood count or FBC.

You may have other blood tests to check:

• how well your kidneys and liver are working
• hormone levels
• your level of vitamin B12

You may be asked to save all the pee you pass in a 24-hour period. Your doctor will then test it for 5HIAA. 5HIAA is made from serotonin by the liver and then passes out of the body in your pee. Certain food, drinks and medicines can raise your levels of 5HIAA. You may need to avoid these for a few days before and during the collection. Your doctor or nurse will tell you more about this.

An ultrasound scan uses soundwaves to build up a picture of the inside of your body. Usually, you can't eat or drink anything for at least 6 hours before the scan. You may also have an ultrasound of your heart, called an echocardiogram.

A CT scan uses X-rays to build a 3D picture of the inside of the body.

An MRI scan uses magnetism to build up a detailed picture of areas of your body.

Nuclear medicine scans use a small amount of a radioactive substance called a tracer. The tracer shows up on the scan pictures. The dose of radioactivity from these scans is low. It's about the same amount you get from an X-ray.

During a biopsy, doctors take a small piece of tissue (or a sample of cells) from a tumour. They then look at it under a microscope. You have a local anaesthetic to numb the area before the sample is taken. Sometimes you have a general anaesthetic for the biopsy, and this depends on where the NET is in your body.

Waiting for test results can be a difficult time. Cancer support services can give you more information that may help.

Depending on the type of neuroendocrine tumour (NET) you have, your doctor may want to do other tests.

A bone scan finds any abnormal areas of bone. A mildly radioactive substance is injected into a vein, and a scan of your bones is taken 2 or 3 hours later.

An endoscopy may also be used. This is when a thin, flexible tube with a camera at the end looks inside the gullet (oesophagus), stomach, small bowel or large bowel.

Your doctor or nurse will explain the test to you and why you need it. Macmillan Cancer Support has more information on cancer tests and waiting for results.

The results of your tests help your doctors find out more about the size and position of the neuroendocrine tumour (NET) and whether it has spread. This is called staging. A doctor decides the grade of the cancer by how the cancer cells look under the microscope, and this gives an idea of how quickly the cancer might grow or spread. Knowing the stage and grade helps your healthcare team plan the best treatment for you.

A team of specialists will meet to decide the best possible treatment for you. This is called a multidisciplinary team (MDT). They'll go through the results of your tests to plan your treatment, and they'll look at factors including:

• where the NET started
• the size of the tumour and whether it has spread (its stage)
• whether you have symptoms of carcinoid syndrome or the over-production of other hormones
• the appearance of the cells under a microscope (its grade)

Your doctor, cancer specialist or nurse will explain the different treatments and their side effects. They'll also talk with you about things to think about when making treatment decisions.

The main treatment for a neuroendocrine tumour (NET) is surgery to remove the tumour. The aim is to cure the cancer. If surgery can't completely remove the NET, treatment will aim to relieve symptoms and improve quality of life.

Your team will plan your operation carefully. They'll explain:

• the surgery
• the possible side effects
• what to expect

If you have a functioning NET, there's a risk that an operation will cause carcinoid crisis. Your doctors will try to prevent this and will monitor you during treatment. Macmillan Cancer Support has more information about preparing for surgery.

Localised and low-grade NETs may be completely removed with surgery, and the aim of the operation is to cure the cancer. Sometimes this type of operation is also possible if there has been only limited spread, which is called regional spread. Depending on where the NET is, it may be possible to remove it during an endoscopy.

For NETs that have spread to the liver, an operation to remove all of the cancer may sometimes be possible. This depends on where the tumours are in your liver, and your doctors will talk it through with you.

If the tumour can't be removed completely, doctors may try to remove as much as they can. This is called debulking. It can improve your symptoms by relieving pressure on other parts of the body. It can also help reduce symptoms caused by the over-production of a hormone.

Surgery can also relieve symptoms when a NET has spread to more distant sites in the body (metastatic). For example, if a tumour is blocking the small bowel, surgery can remove it or bypass the blockage.

There are other treatment options you may have.

Some neuroendocrine tumours (NETs) are slow-growing and may not change for months or years. If a NET spreads but isn't causing symptoms, you may not need treatment straight away. Your doctor will monitor you with regular check-ups, and if symptoms develop, you'll have the option of treatment.

Somatostatin analogues are drugs that treat the symptoms of carcinoid syndrome. They work by blocking the hormones the tumour makes. They may also control the growth of NETs. You may be given them along with other treatments.

Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. You may have chemotherapy to treat NETs that have spread. The type you'll have depends on where the NET started in the body.

Chemotherapy treatments that can be used for NETs include:

• capecitabine and temozolomide (CAPTEM)
• FOLFOX
• streptozocin and fluorouracil (5FU)
• etoposide and cisplatin (EP)
• carboplatin and etoposide

Targeted therapies

Targeted therapies are anti-cancer medicines that interfere with how cancer cells grow and divide. The 2 main targeted therapy drugs used are:

• sunitinib (Sutent®)
• everolimus (Afinitor®)

You take these drugs as capsules or tablets. Other targeted therapies may be available as part of a clinical trial.

Interferon is a drug that can treat the symptoms of NETs. It may also control how the tumour grows. Interferon is a protein that you naturally have small amounts of in your body. If you have it as a drug, it can stimulate the body's immune system to destroy cancer cells. You'll have it as an injection under the skin.

Radiotherapy uses high-energy x-rays to destroy cancer cells, while doing as little harm as possible to normal cells. You may have radiotherapy if it's not possible to remove the tumour with surgery, or if it has already spread.

You may have radionuclide therapy to relieve symptoms of carcinoid syndrome and control the growth of NETs. This therapy uses a radioactive substance called a radionuclide. It's injected into the bloodstream.

Some treatments go straight to the liver, and they can sometimes be used for neuroendocrine tumours (NETs) that have spread there.

One of these is hepatic artery embolisation. It can sometimes shrink NETs in the liver, and it can also relieve the symptoms of carcinoid syndrome. It works by cutting down the blood flow to the tumours, because tumours need a blood supply to survive.

Radiofrequency ablation (RFA) can also treat NETs in the liver. It uses laser or radio waves to heat the cancer cells to high temperatures, which destroys them.

Selective internal radiation therapy is another option. This is a type of cancer treatment that uses tiny radioactive beads, and it can treat NETs found in the liver.

You'll have regular follow-up appointments after your neuroendocrine tumour (NET) treatment. Your doctors may keep a check on you with blood tests and scans.

Some people are cured of NETs after treatment. Others carry on having treatment whenever they need it, to help keep the cancer under control.

If the cancer is advanced, there are different things that can be done to support you by controlling the symptoms.

Even if you already live a healthy life, you may want to make some positive changes during and after treatment for neuroendocrine tumours. If you smoke or drink alcohol, it's best to avoid smoking and to cut down on how much alcohol you drink.

Eating well and staying active can improve your health and wellbeing, and they can help your body recover too. If you have any difficulty with eating after treatment, your dietitian can help.