Also known as:
- Neuroendocrine neoplasms (NENs)
- Neuroendocrine carcinomas (NECs)
- Carcinoid tumours
A word about naming.
This is a very large and diverse group of tumours affecting many different organs with no typical pattern of behaviour. They are all named neuroendocrine tumours (NETs) after the basic type of cell that they form in. The specific name given to a neuroendocrine cancer could refer to:
- The organ it started in
- e.g pancreatic NET
- The exact cell type it started in
- e.g. Schwannoma is a neuroendocrine cancer in the nervous system
- What it makes (many NETs produce excess hormones)
- e.g. insulinoma makes excess insulin
What it is not.
NETs are not “types” of other cancers. A neuroendocrine tumour of the lung is not a type of lung cancer, it doesn’t start within lung cells. A neuroendocrine tumour of the pancreas, is not pancreatic cancer. They have different symptoms and treatments.
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How rare are neuroendocrine tumours?
In the UK and Europe the usual definition of a rare cancer is one that occurs in less than 6 people out of every 100,00 each year. Because there are around 200 rare cancers, this means that they make up about 24% (nearly a quarter) of all cancers.
The incidence of all NETs is 2.53 per 100,000, making individual NETs very rare, the most common are found in the lungs and digestive system.
They are seen in people of all ages, but the most common age for diagnosis is between 66 and 70, although this probably reflects the slow development of many of these cancers. They are also slightly more common in people with a white background and women, although it is not known why. The incidence of individual neuroendocrine cancers is summarised in the separate information sheets.
What is NETs?
Unlike the more familiar organs of the body such as brain, lungs and stomach, neuroendocrine cells and the neuroendocrine system are less well known.
What are neuroendocrine cells?
In order for our bodies to function correctly, messages have to be sent between different organs and tissues, for example telling it to move an arm, to make more digestive juices in response to food or to take sugar out of the bloodstream.
These messages can be sent as fast signals through the nerves of your nervous system (e.g. moving your arm), or more slowly through the release of hormones by glands of the endocrine system such as your pancreas.
Sometimes a signal is sent via the nerves from the brain to an organ so that particular cells will then make a hormone to do a particular job. For example when we are in a scary or threatening situation the brain sends messages down the nerves to the adrenal glands (on the outside edge of the kidney) which release adrenaline, the hormone that prepares your body for action.
The cells that receive nerve signals and release hormones are called neuroendocrine cells (neuro – means to do with nerves, endocrine means to do with hormones). All of the cells and organs that do this together are called the neuroendocrine system.
These cells are found all over the body, forming part of organs like the stomach, pancreas, kidneys and lungs. Sometimes an organ has just a few neuroendocrine cells, sometimes it is almost entirely made of neuroendocrine cells. The pituitary gland in the brain is one of these. It is often called the master gland as it makes many different hormones that affect much of the body.
There are two big families within the blood cells. The myeloid cells on the left and the lymphoid cells on the right. These may sound familiar if you have met the different leukaemias.
CML (chronic myeloid leukaemia) and AML (acute myeloid leukaemia) affect white blood cells that form from the myeloid side of the family – the granulocytes (also known as neutrophils) and the monocytes.
Notice their “cousin” the erythrocyte or red blood cell. These can also develop a rare cancer called polycythaemia vera. On the other side of the family tree are the lymphoid cells that produce the B and T lymphocytes or white blood cells. When these develop into cancer they are called lymphocytic leukaemia. CLL (chronic lymphocytic leukaemia) comes from the B-cells and ALL (acute lymphocytic leukaemia) from either T or B cells. There are different types of ALL depending on whether B or T cells are affected.
What are hormones?
Hormones act as chemical messengers in the, delivering instructions for particular cells, tissues or organs. Hormones are a mixed bag of molecules, some are proteins, some are another type of molecule called a steroid.
When hormones are released into the bloodstream they travel around the body. To make sure that only the right cells respond to a particular hormone, they have molecules on the surface called receptors. You can think of them like a specially shaped lock. If the hormone fits the receptor, like a key, it triggers a response in that cell. For example, if the hormone is insulin, it triggers muscle and liver cells to take up glucose from the blood. If it is a hormone called FSH (follicle stimulating hormone) it triggers the development of an egg cell in a woman’s ovary. The production and response to hormones is normally very tightly controlled by the body.
What is Neuroendocrine Cancer?
Neuroendocrine cancers occur when some neuroendocrine cells begin to divide uncontrollably. The signs and symptoms of each neuroendocrine cancer depend on the type of cell involved. Symptoms may be caused by the presence of a tumour blocking a tube (e.g. airway) or pressing on its original, or a nearby organ. Symptoms can also be caused by the changes in hormones produced by the tumour.
Particular types of neuroendocrine cells are more prone to developing cancer. These can be found in the diagram below. There are separate detailed summaries for the main types of NETs.
Image from Cancer Research UK.
Describing different types of NET behaviour.
Because neuroendocrine cells release hormones, when they become cancerous they may release more or less hormone than before. This affects whether or not the cancer produces certain symptoms. It also affects the way it is treated. The effects of too little or too much hormone may need to be treated alongside the cancer.
- If the cancer produces hormones it is called a functional neuroendocrine tumour.
- If it does not produce hormones, or very little, it is called a non-functional endocrine tumour.
NETs can also be described as being “indolent” or “aggressive”. An indolent person is lazy, avoids doing anything or putting in effort. An indolent NET will grow slowly, look very similar to normal cells and be less likely to spread (metastasise). They are sometimes described as carcinoid or (cancer-like).
An aggressive NET is the opposite. It will look very different from its original cell type, be fast growing and more likely to spread.
Risk factors:
There are a number of inherited genes that increase the risk of certain neuroendocrine cancers. The MEN set of mutations, von-Hippel-Lindau syndrome and neurofibromatosis type 1 are associated with increased risks. There is a connection with having a family history of cancer, particularly lung cancer, although it is not known if the effect is genetic, or from living in a similar environment. As is the case with many cancers, smoking increases the risk of developing NETs.
A family of neuroendocrine cancers.
(Please click on the link for more information about NETs from different locations).
Gastro-intestinal – NETs of the digestive system. These are the commonest type (about 44% of all NETs) Including the large intestine, small intestine and appendix.
Lung – about 30% of all NETs start here. Mostly they form in the bronchial system – the larger tubes that take air to the lungs.
Pancreatic – most of these are non-functional and rarely produce symptoms at an early stage. Others produce a range of hormones.
Thyroid gland – usually known as medullary thyroid cancer. About a quarter of these are inherited.
Adrenal gland – also called pheochromocytoma and paraganglioma.
Pituitary gland – often called PitNETS for short.
Liver and gallbladder
Reproductive organs
Skin
Nervous system
What are the current treatment options for NETs?
This is entirely dependent on the type and behaviour of your particular neuroendocrine tumour.
One way of assessing cancer cells is their differentiation. This is how like the original cells they are. Well differentiated tumours still look and behave a lot like their original cell type. These are generally less likely to grow quickly or spread . Poorly differentiated or undifferentiated cells look very unlike their original cell type and are more likely to be fast growing.
If the tumour is slow-growing and well differentiated there may be no need for any treatment other than “watchful waiting”, where the tumour is checked regularly for any change.
If treatment is needed it will depend on what type of NET it is and if it has spread. Surgery, chemotherapy, radiotherapy, immunotherapy or targeted therapy can be used along with treatments to deal with the consequences of excess hormone production (carcinoid syndrome).
For more information, see the pages for individual NET types.
What are the current clinical trials for NETs?
There are 9 trials open in the UK which include patients with NETs (as of 11/11/22). 8 investigational drugs are currently being tested. Not all of these will be suitable for all NETs.
The language used to describe these trials includes a lot of scientific terms. If you are invited to join a trial your medical team will explain what these treatments do in more detail.
- Entrectinib (RXDX-101, NMS-E628) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor.
- A targeted therapy that stops cancer cells receiving chemical messages that make them grow
- Selpercatinib is an inhibitor of the RET (rearranged during transfection) receptor tyrosine kinase.
- A targeted therapy that stops cancer cells receiving chemical messages that make them grow.
- BXCL701 (talabostat), is an oral small molecule inhibitor of dipeptidyl peptidases (DPP)—primarily DPP 8/9 & DPP which triggers inflammasome to alert and prime immune cells, leading to induction of IL-18 & IL-1ß, bridging innate & adaptive immunity.
- Talabostat helps the immune system to recognise and destroy cancer cells.
- Surufatinib (HMPL-012, previously known as sulfatinib) is a new, oral, small-molecule tyrosine kinase inhibitor that potently inhibits vascular endothelial growth-factor receptor 1–3, fibroblast growth-factor receptor 1, and colony-stimulating-factor-1 receptor. This unique combination of molecular activities inhibits tumor angiogenesis, regulates tumor-immune evasion, and may decrease tumor resistance.
- This is a multi-tasking drug that stops tumours growing their own blood supplies and helps the immune system to find and destroy cancer cells.
- Tarlatamab (AMG 757), a DLL3-targeted immunotherapy
- Helps to activate the immune response
- Lutetium LU 177-edotreotide- A radioconjugate consisting of the somatostatin analogue edotreotide labeled with lutetium Lu 177 with potential antineoplastic activities. Lutetium Lu 177-edotreotide binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor cells.
- Somatostatin is a hormone that turns down the strength of hormonal responses, several drugs have been made that mimic the action of somatostatin. Adding a radioactive atom makes it more effective.
- Belzutifan– a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor
- A targeted therapy for people with Von-Hippel gene mutation
- Debio 4126 is sustained-release formulation designed to improve the performance and convenience of somatostatin analogue (SSA) therapy.
Where can I find CLL support groups?
Name
Website
Notes
Neuroendocrine cancer UK
Main UK support group with a range of useful patient information leaflets. Starting to fundraise for research projects.
A site by Ronny Allan – Living with neuroendocrine cancer
A very high profile blogger and patient advocate with NEC. You can join his facebook support group from his excellent website.
AMEND
Support and information for patients with cancers of endocrine system (glands) e.g. thyroid, parathyroid, adrenal and the inherited condition MEN.
Awareness and symbols
World NET awareness day is held on 10th November. It is coordinated by the International Neuroendocrine Alliance.
The ribbon for NET cancers is a zebra print.
Image from Wikimedia Creative Commons.
Why a zebra?
Try this thought experiment. You hear hoofbeats coming towards you – what could it be? It’s reasonable to assume it’s a horse. Horses are very common in most places. It’s highly unlikely that the source of the sound is a zebra.
But just occasionally, it really is a zebra.
This is often the situation with NETs. Rare, unexpected and something doctors need to consider when dealing with symptoms that may point to other causes.
