Neuroendocrine tumours (NETs)

Neuroendocrine tumours (NETs) are uncommon. They develop from cells of the neuroendocrine system. These are found in organs such as the stomach, bowel and lungs.

NETs are more common in people aged over 60. They are sometimes called carcinoid tumours.

Symptoms depend on where in the body the NET is. They can include:

  • tummy pain
  • changes in bowel function
  • flushing of the skin
  • shortness of breath
  • loss of appetite
  • weight loss.

To help diagnose a NET, you may have a variety of tests. These can include urine or blood tests, a biopsy, and different scans.

Treatment depends on:

  • where the NET started
  • the size of the NET
  • whether the NET has spread
  • how the cells look under a microscope
  • your symptoms.

The main treatment is surgery to remove the tumour. If surgeons cannot remove the NET, your treatment will aim to stop your symptoms and improve your quality of life.

Some NETs are slow-growing and may not change for some time. If the NET is not causing any symptoms, you may not need treatment straight away. Your doctors will monitor you and offer treatment if symptoms develop.

What are neuroendocrine tumours (NETs)?

A neuroendocrine tumour (NET) is a tumour that develops from cells of the neuroendocrine system. Cells that are similar to nerve cells make up the neuroendocrine system. They make chemical messengers called hormones. Hormones control how different organs in the body work.

Neuroendocrine cells are found throughout the body, in organs such as the stomach, bowel and lungs.

NETs can be non-cancerous (benign) or cancerous (malignant). This information is about malignant tumours. It is mainly about NETs affecting the digestive system.

Some NETs make extra hormones and cause symptoms. These are called functioning tumours. Tumours that do not make extra hormones are called non-functioning tumours.

NETs are grouped according to where the cancer started (the primary tumour). For example:

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

Rarely, NETs occur in other areas, including the:

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

You may hear some NETs referred to as carcinoid tumours. These are usually tumours of the digestive system or lungs.

NETs often grow slowly. They can be difficult to diagnose, as they may not cause symptoms for a long time. It may be several years before symptoms appear and the tumour is diagnosed. But some NETs grow faster and are more likely to spread to surrounding tissues and parts of the body.


Causes and possible risk factors of NETs

NETs are uncommon. We do not know what causes them.

These tumours are most likely to affect people over the age of 60. People with a rare condition called multiple endocrine neoplasia 1 (MEN1) have a higher risk of developing NETs.


Signs and symptoms of NETs

Symptoms will depend on where in the body the NET is.

Symptoms of a NET in your digestive system include:

  • pain or discomfort in the tummy area (abdomen) that comes and goes
  • feeling sick (nausea) or being sick (vomiting)
  • diarrhoea
  • heartburn and indigestion.

A NET in the lung may cause:

  • chest infections
  • shortness of breath
  • a cough
  • coughing up blood.

Loss of appetite and weight loss may also be symptoms of a neuroendocrine tumour.

NETs sometimes make too much of certain hormones. When they are released into the blood stream, they cause symptoms. These NETs are called functioning tumours. The type of hormone they make depends on which gland the tumour is affecting.

Carcinoid syndrome

Some NETs may produce too much of a hormone-like substance called serotonin. This is more common in NETs of the small bowel, large bowel or appendix. It causes a collection of symptoms called carcinoid syndrome.

Symptoms include:

  • diarrhoea
  • the skin on your face and upper chest feeling hot and changing colour (flushing), ranging from pink to purple.
  • wheezing (similar to asthma)
  • tiredness (fatigue).

To help control these symptoms, you might need to avoid things that trigger flushing. These may include drinking alcohol or eating spicy food. You may also be able to reduce diarrhoea by making changes to your diet. A specialist dietitian can advise you about this.

Sometimes, the symptoms of carcinoid syndrome can be particularly bad. You may have severe diarrhoea, flushing, abdominal pain and palpitations. This is called carcinoid crisis. Being under stress, having a general anaesthetic and receiving other treatments can all trigger carcinoid crisis. This is a potentially serious condition and will need treatment. To help prevent carcinoid crisis, doctors will monitor you carefully during medical procedures or treatment.

Carcinoid heart disease

Sometimes, both serotonin and another substance the NET produces (called tachykinin) can affect the heart. This can cause carcinoid heart disease. The main symptoms are:

  • breathlessness
  • swollen ankles.

You should see your GP if you develop these symptoms or if they are getting worse.


Other NETs that cause symptoms

There are other NETs that can overproduce hormones and can cause specific symptoms. These include:

  • insulinomas
  • gastrinomas
  • glucagonomas
  • VIPomas
  • somatostatinomas

Insulinomas

Insulinomas are tumours that can develop in any part of the pancreas. The pancreas makes insulin, which controls the level of sugar in the blood. If you have an insulinoma, the tumour makes an unusually high level of insulin. This causes low blood sugar levels (hypoglycaemia).

A low blood sugar level may cause symptoms such as:

  • headaches and dizziness
  • confusion and anxiety
  • trembling and palpitations
  • eyesight changes
  • feeling hungry or weak
  • fits (seizures).

A low blood sugar level is most likely to occur:

  • first thing in the morning
  • when exercising
  • after missing a meal.

Often eating or having a sugary drink will raise the blood sugar level again.

Gastrinomas

Gastrinomas are tumours that usually start in the pancreas or the upper part of the small bowel (duodenum). They sometimes make too much gastrin. Gastrin is a hormone that controls the amount of gastric acid that the stomach makes.

Too much gastrin causes the stomach to make more gastric acid. High levels of gastric acid can lead to sores (ulcers) in the stomach, the gullet (oesophagus) and the small bowel. There may be several ulcers. Often, these do not respond well to the usual medicines. This is often called Zollinger-Ellison syndrome.

Common symptoms of a gastrinoma include:

  • feeling bloated or pain in the tummy area (abdomen)
  • diarrhoea
  • heartburn
  • weight loss
  • bleeding into the stomach
  • feeling sick (nausea) or being sick (vomiting).

Glucagonomas

These tumours are usually in the pancreas. They usually make too much glucagon, a hormone that helps control blood-sugar levels.

Common symptoms of a glucagonoma include:

  • anaemia (a low level of red blood cells)
  • weight loss
  • high blood-sugar (hyperglycaemia)
  • a skin rash
  • diarrhoea
  • blood clots.

VIPomas

These tumours are usually in the pancreas. They may make too much of a substance called vasoactive intestinal peptide (VIP).

Common symptoms of a VIPoma include:

  • watery diarrhoea
  • low levels of potassium because of the diarrhoea
  • feeling weak and tired
  • feeling sick (nausea) and being sick (vomiting).

Somatostatinomas

Somatostatinomas are rare tumours. They are usually in the pancreas or parts of the small bowel (the duodenum or jejunum). They make extra somatostatin. This is a hormone that stops the pancreas producing other hormones. Somatostatin also affects how the digestive system works.

Common symptoms of a somatostatinoma include:

  • pain in the tummy area (abdomen)
  • weight loss
  • pale, greasy and offensive-smelling poo (steatorrhoea)
  • diarrhoea
  • high blood-sugar (diabetes)
  • yellowing of the skin and whites of the eyes (jaundice).


NETs that do not cause symptoms

Some tumours do not overproduce hormones and may not cause symptoms. These are known as non-functioning NETs. They may show up during operations or tests that you are having for other reasons.


How NETs are diagnosed

You usually start by seeing your GP. If they are unsure of the problem, they will 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 will then examine you and talk to you about the tests you need to have.

Sometimes, NETs show up on a scan you may be having for another reason.

Urine tests

Some NETs increase the amount of serotonin in the body. Serotonin is a chemical the body makes that sends messages between different parts of the brain. It helps control lots of functions, such as how you sleep, your mood, and your appetite. The liver changes serotonin into a chemical called 5HIAA. The body then passes 5HIAA out through the urine.

You will be asked to save all the urine you pass in a 24-hour period. Your doctor will then test it for 5HIAA.

Certain foods, drinks and medicines can raise your levels of 5HIAA. You may need to avoid these for a few days before and during the urine collection.

Blood tests

If you have a NET, the levels of some chemicals in the blood may rise. This is especially true for serotonin and chromogranin A (CgA). You will need to give blood samples to check the levels of these chemicals.

You will also have a blood test to count the number of healthy blood cells in your blood. This is called a full blood count or FBC. Another blood test will check how well your kidneys and liver are working.

Ultrasound scan

This uses soundwaves to build up a picture of inside your body. Usually, you cannot eat or drink anything for at least 6 hours before the scan. You will lie comfortably on your back and a gel is spread onto your tummy (abdomen). A small device that produces sound waves is then passed over the area. The sound waves produce a picture on a computer. The test is painless and only takes a few minutes.

You may also have an ultrasound of your heart, called an echocardiogram (ECG).

CT (computerised tomography) scan

A CT scan takes a series of x-rays, which build up a three-dimensional picture of the inside of the body. The scan takes 10 to 30 minutes and is painless. It uses a small amount of radiation, which is very unlikely to harm you and will not harm anyone you come into contact with.

CT scan
CT scan

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You may be given a drink or injection of a dye, which allows particular areas to be seen more clearly. This may make you feel hot all over for a few minutes. It is important to let your doctor know if you are allergic to iodine or have asthma, because you could have a more serious reaction to the injection.

You will probably be able to go home as soon as the scan is over.

MRI scan

This test uses magnetism to build up a detailed picture of areas of your body. The scanner is a powerful magnet so you may be asked to complete and sign a checklist to make sure it is safe for you. The checklist asks about any metal implants you may have, such as a pacemaker, surgical clips or bone pins, etc.

You should also tell your doctor if you have ever worked with metal or in the metal industry as very tiny fragments of metal can sometimes lodge in the body. If you do have any metal in your body, it is likely that you will not be able to have an MRI scan. In this situation, another type of scan can be used. Before the scan, you will be asked to remove any metal belongings including jewellery.

Some people are given an injection of dye into a vein in the arm, which does not usually cause discomfort. This is called a contrast medium and can help the images from the scan to show up more clearly. During the test, you will lie very still on a couch inside a long cylinder (tube) for about 30 minutes. It is painless but can be slightly uncomfortable, and some people feel a bit claustrophobic. It is also noisy, but you will be given earplugs or headphones. You can hear, and speak to, the person operating the scanner.

Nuclear medicine scans

You may have these tests to find where the cancer started (the primary tumour). Or they may check for any spread of the disease (secondaries or metastases). The tests use a small amount of a radioactive substance called a tracer. The tracer shows up on scan pictures.

The dose of radioactivity from these scans is low. It is about the same amount you get from an x-ray. Almost all of it leaves your body within a week. The staff in the scanning department will tell you about any precautions you need to take after the scan.

If you plan on travelling abroad within three months of the scan, tell the doctor in the scanning department. They can give you a letter to show that you had a radioactive scan. This is because ports and airports have sensitive machines that pick up tiny amounts of radioactivity.

Octreotide scan

Neuroendocrine tumours often absorb a substance called octreotide. Doctors can attach a radioactive tracer to octreotide. This is so it can show up on scan pictures. They then inject the octreotide into the bloodstream. The scan pictures show areas of the body where radioactivity collects.

You will have three scans. You will have one on the day of the injection. You will then have two more over the next two days. You will have to keep still while the scanner takes pictures. Each scan takes about 30 minutes. You can go home between the scans.

An octreotide scan is sometimes called an Octreoscan or somatostatin receptor scintigraphy.

MIBG scan

NETs can also absorb a substance called MIBG. A radioactive tracer can be attached to MIBG, just like octreotide. This means you can have a scan that uses MIBG in a similar way to octreotide.

Ga68 PET-CT scan

This is similar to an octreotide scan, but more sensitive. You will have an injection containing the radioactive tracer gallium 68 DOTANOC. An hour later, you will have a PET/CT scan (see below). The scan takes about 30 to 45 minutes.

PET-CT scan

This is a combination of a CT scan, which takes a series of x-rays to build up a three-dimensional picture, and a positron emission tomography (PET) scan. A PET scan uses low-dose radiation to measure the activity of cells in different parts of the body.

PET-CT scans give more detailed information about the part of the body being scanned. You may have to travel to a specialist centre to have one. You cannot eat for six hours before the scan, although you may be able to drink. A mildly radioactive substance is injected into a vein, usually in your arm. The radiation dose used is very small. You will wait for at least an hour before you have the scan. It usually takes 30 to 90 minutes. You should be able to go home after the scan.

Biopsy

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. This depends on where the NET is in your body. Your doctor will explain how they will do the biopsy.

Other tests

Depending on the type of NET you have, your doctor may want to do other tests, including:

  • a bone scan
  • an endoscopy – using a thin, flexible tube with a camera at the end to look inside the gullet, stomach, small bowel or large bowel.

Your doctor or nurse will explain the test to you and why you need it.

Someone having a CT scan

Having a CT scan

A radiographer explains how a CT scan works, and Jyoti talks about her experience.

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Having a CT scan

A radiographer explains how a CT scan works, and Jyoti talks about her experience.

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Staging and grading of NETs

Staging

The stage of a cancer describes its size and whether it has spread beyond its original site. Knowing the stage of the cancer helps the doctors decide the best treatment for you.

There is no standard staging system for NETs, but doctors may divide them into three stages:

  • Localised – the cancer is contained inside the organ where it started. For example, this could be the appendix, bowel or stomach.
  • Regional spread – the cancer is growing through the wall of the organ into nearby tissues. It may also have spread to nearby lymph nodes.
  • Distant spread (metastatic) – the cancer has spread to other parts of the body, such as the liver, bones or lungs.

Grading

Grading describes how tumour cells look under a microscope. It shows how abnormal the cells are. It can give an idea of how quickly the tumour may develop. This helps the doctors decide on the best treatment for you.

The grade of a NET depends on:

  • how quickly cells divide to make new tumour cells (called the mitotic count)
  • the amount of protein (called Ki-67) cells make when they divide
  • how many dead cells there are (necrosis).

NETs are usually divided into three groups:

  • Well differentiated – the cells look like normal cells and are usually slow-growing.
  • Moderately differentiated – the cells look more abnormal.
  • Poorly differentiated – the cells look very abnormal. They are likely to grow more quickly and spread.


Treatment for NETs

A multi-disciplinary team (MDT), will manage your treatment. This is a group of healthcare professionals with expert knowledge in treating NETs. They will discuss the results of your tests to plan your treatment. They will 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).

The main treatment is surgery to remove the tumour. The aim of this is to cure the cancer. If surgery cannot completely remove the NET, treatment will aim to relieve symptoms and improve quality of life.

Some NETs are slow-growing and may not change for months or years. If a NET spreads but is not causing symptoms, you may not need treatment straight away. Your doctor will monitor you with regular check-ups. You will have the option of treatment if symptoms develop. This treatment approach is sometimes called ‘watchful waiting’.

Surgery

Localised NETs can often be completely removed. The aim of the operation is to cure the cancer. Sometimes, this type of operation is possible if there has been only limited spread (regional spread).

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

An operation to remove all of the cancer may sometimes be possible for NETs that have spread to the liver. This will depend on how it is affecting your liver. Your doctors will discuss this with you.

Surgery can also help relieve symptoms of a NET that 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.

If you have a functioning NET, there is a risk that an operation can cause carcinoid crisis. Your doctors will take precautions to help prevent this and they will monitor you during treatment.

Somatostatin analogues

Somatostatin analogues are drugs that treat the symptoms of carcinoid syndrome. They can help reduce flushing and diarrhoea. They work by stopping the body making too many hormones. They may also control the growth of NETs.

The most commonly used somatostatin analogues are:

  • octreotide (Sandostatin®, Sandostatin Lar®)
  • lanreotide (Somatuline® LA, Somatuline Autogel®).

You will usually have the first few injections as an outpatient. They are given under the skin (subcutaneously) or into a muscle. You could have them:

  • up to 3 times a day, every day
  • once every 7 to 14 days
  • once every 28 days.

This will depend on your how symptoms respond to the treatment. Most people will have the injection every 28 days. A district nurse or practice nurse can give you the injections at home. Sometimes the nurse can show you, or a relative or friend, how to do the injections.

Chemotherapy

Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. You may have chemotherapy to treat NETs that have spread. The aim is to shrink the tumour and reduce symptoms.

The type of chemotherapy you will have depends on where the NET started in the body.

Your doctor and specialist nurse will give you more information about chemotherapy and any side effects you may have.

Targeted therapies

Targeted therapies are anti-cancer medicines that interfere with how cancer cells grow and divide. They are sometimes called biological therapies.

Targeted therapies are sometimes used to treat certain types of NET. The two main targeted therapy drugs used are:

You take these drugs as capsules or tablets.

Your doctor can advise whether you can have a targeted therapy and what side effects you may have.

Interferon alpha (IntronA®)

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 will have it as an injection under the skin.

Interferon can cause flu-like symptoms including chills, fever, aching joints and tiredness. But these side effects usually lessen after a few weeks.

Sometimes you will have interferon combined with somatostatin analogues.

Radiotherapy

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 is not possible to remove the tumour with surgery, or if it has already spread.

You can have radiotherapy externally from a radiotherapy machine (called external beam radiotherapy). Or you can have it internally by placing radioactive material close to the tumour (called brachytherapy).

External beam radiotherapy usually treats symptoms such as pain, if the tumour has spread to the bones.

Targeted radionuclide therapy

You may have this to relieve symptoms of carcinoid syndrome and control the growth of NETs.

This therapy uses a radioactive substance called a radionuclide. It is injected into the bloodstream. Cancer cells absorb the radionuclide more than normal cells. This means they receive a higher dose of radioactivity. This eventually destroys the cancer cells.

To control the growth of NETs, the radioactive substance can be combined with either octreotide or MIBG. The NET cells absorb the drug along with the radioactive substance.

If the treatment uses octreotide, it is sometimes called peptide receptor radionuclide therapy (PRRT).

Targeted radionuclide therapy only works for NETs that absorb large amounts of octreotide or MIBG. So before treatment, you will have a scan. The scan will measure how much octreotide or MIBG the tumour absorbs.

After the radionuclide therapy, you will need to be in a room by yourself for a few days. This is so the radiation cannot affect others, especially children and pregnant women. Your nurse will give you more information about this.

Some people get a tummy ache or feel sick because of the treatment. Medicines can help with this. There may be a temporary drop in some of your blood cell levels. If this happens, you may feel tired, be more at risk of infection, or bruise or bleed more easily. But doctors will monitor you closely.

For most people, the side effects do not last long and they recover quickly.

Chemotherapy

This video provides a brief overview of chemotherapy treatment, how it can be given, how it works and possible side effects.

About our cancer information videos

Chemotherapy

This video provides a brief overview of chemotherapy treatment, how it can be given, how it works and possible side effects.

About our cancer information videos

How targeted therapies work

This animation shows how targeted therapies work and what effect they have on the body.

About our cancer information videos

How targeted therapies work

This animation shows how targeted therapies work and what effect they have on the body.

About our cancer information videos


Treatments for NETs in the liver

Treatments that directly target the liver can sometimes treat NETs in the liver. These treatments include hepatic artery embolisation and radiofrequency ablation.

Hepatic artery embolisation

A hepatic artery embolisation can sometimes shrink NETs in the liver. It can also relieve the symptoms of carcinoid syndrome. Tumours need a blood supply to survive. Hepatic artery embolisation works by reducing blood flow to the tumours.

The doctor gently puts a thin tube into the main blood vessel in your groin (the femoral artery). Guided by a scan, they slowly feed the tube into the main blood vessel of the liver (the hepatic artery). They then inject a drug that blocks the blood supply (embolises it).

Sometimes the drug is combined with chemotherapy. This is called chemoembolisation. The highly concentrated chemotherapy stays in the tumour to kill some of the cells and shrink the tumour. Chemoembolisation is sometimes called TACE (trans-arterial chemoembolisation) or CT-ACE (computerised tomography guided arterial chemoembolisation).

You will probably stay in hospital overnight. You may feel sick, have tummy (abdominal) pain and a high temperature for a few days afterwards. Your doctor or nurse can give you more information.

Radiofrequency ablation

Radiofrequency ablation (RFA) can treat NETs in the liver. It uses laser or radio waves to destroy the cancer cells by heating them to high temperatures.

You will have a sedative to make you feel drowsy and relaxed. Next, the doctor uses a local anaesthetic to numb the skin of your tummy (abdomen). They then insert a fine needle through the skin and into the centre of the tumour in the liver. Powerful laser light or radio waves pass through the needle and into the tumour. This heats the cancer cells and destroys them.

You will probably stay in hospital overnight. You may feel sick, have tummy (abdominal) pain and have a high temperature for a few days afterwards. Your doctor or nurse can give you more information.

Selective internal radiation therapy (SIRT)

Selective internal radiation therapy is a type of cancer treatment that uses tiny radioactive beads. It can treat secondary tumours (metastases) in the liver.

Tumours in the liver get most of their blood supply from a blood vessel called the hepatic artery. For treatment with SIRT, your doctor will put a thin tube (catheter) into this blood vessel. They then inject radioactive beads into the catheter. The beads travel into the smaller blood vessels that supply the tumour. The beads deliver radiation to the cancer cells, causing little damage to healthy liver tissue.

SIRT is not available in all UK hospitals, so you may have to travel to have the treatment. Your doctor will arrange for tests to decide whether SIRT is suitable for you.

We have more information about SIRT.

Cancer research trials

Cancer doctors use cancer research trials to assess new treatments. Current studies are looking at new treatments for NETs. Your doctor may ask you to take part in a cancer research trial. They will discuss the treatment with you, so you understand the trial and what it means to take part.


Your feelings

You may have many different emotions, including anxiety, anger and fear. These are all normal reactions. They are part of the process that many people experience when dealing with cancer.

Everyone has their own way of coping with difficult situations. Some people find it helpful to talk to family or friends. Others may prefer to seek help from people outside their situation. Some people prefer to keep their feelings to themselves. There is no right or wrong way to cope, but help is there if you need it. Our cancer support specialists and other organisations, like the NET Patient Foundation, can give you information about counselling in your area.

Back to Understanding pancreatic cancer

What is cancer?

There are more than 200 different kinds of cancer, each with its own name and treatment.

What is the pancreas?

The pancreas is part of the digestive system. It is in the upper part of the tummy (abdomen).

Types of pancreatic cancer

Pancreatic cancers can be described by where they are found in the pancreas or the type of cells they start from.

Symptoms of pancreatic cancer

Pancreatic cancer may not cause symptoms for a long time. Common symptoms are pain or discomfort, jaundice and weight loss.