Neuroendocrine & Carcinoid Tumors

Introduction

Neuroendocrine tumors (NETs) are slow-growing tumors that begin in neuroendocrine cells. These cells have 2 interesting qualities. They have nerve-cell traits, and they can create hormones. Most NETs tend to develop over many years and may be hard to diagnose.

Not all NETs are cancers, but some can become cancerous and spread to other organs. Based on their grade, they can vary from very slow-growing to extremely fast-growing cancers. The grade is assigned by a pathologist who looks at the tumor under a microscope. They’re all named by where they begin (like GI-NET or pancreatic-NET). NETS may form in various organs. These might include the:

  • Lungs
  • Digestive system
  • Endocrine organs (the thyroid, adrenal gland, pituitary gland, thymus)
  • Skin

Types of NETs

NETs can be classified based on their ability to produce hormones. Functional NETs secrete hormones, while non-functional NETs do not secrete hormones.

NETs can be called well-differentiated if the cancer cells look like normal cells. Cells that are poorly differentiated look less like normal cells.

The most common NETs are:

  • Carcinoid tumors: Well-differentiated NETs that begin in the gastrointestinal (GI) tract or lungs. They can also be seen in the gonads (ovaries and testes) or skin. Some secrete a hormone called serotonin, but most do not secrete any hormones.
  • Pancreatic neuroendocrine tumors: Well-differentiated NETs that begin in the pancreas. Some produce hormones like insulin, glucagon, gastrin, VIP, and somatostatin, whereas others are non-functional.
  • Pheochromocytoma: A rare NET that can develop in the adrenal gland or other parts of the body. They produce too many of the “fight-or-flight” hormones (like adrenaline), causing high blood pressure.

Risk Factors

Environmental risks that can cause NETs are currently unknown. Some risk factors may include:

  • Age: Most people are diagnosed over age 60.
  • Race and sex: Women and African Americans are diagnosed more often.
  • Smoking.
  • Diet: A high-fat, high-sugar diet adds to risk.

Signs & Symptoms

Symptoms are caused by the location of the tumor and if the tumor secretes hormones. As mentioned previously, tumors are either functional or non-functional.

Functional tumors: When NETs produce abnormal hormones, peptides, and proteins, so the body reacts badly. Some mid-gut and foregut NETs (especially small bowel NET and lung NET) can produce excessive serotonin, resulting in carcinoid syndrome.

Signs of carcinoid syndrome:

  • Flushed skin (the skin turns red and hot in flashes; purplish veins show on the face) 
  • Diarrhea
  • Abdominal pain
  • Wheezing
  • Changes in blood pressure
  • Low or high blood sugar

Certain pancreatic functional NETs can produce excess hormones like insulin, VIP, and gastrin, resulting in respective syndromes:

  • Insulinoma syndrome (low blood sugar)
  • VIPoma syndrome (diarrhea)
  • Zollinger-Ellison syndrome (stomach ulcers)

Non-functional tumors: When NETs don’t produce anything, but the mass or tumor bulk causes problems. In the gut or bowel, NETs can cause an obstruction and belly pain. Close to or inside the lung, carcinoid tumors can cause breathing problems, chest pain, and coughing. Based on the location of the tumor, other symptoms may include:

  • Nausea and vomiting
  • Inability to pass stool (bowel obstruction)
  • Pain
  • Rectal bleeding
  • Sweating, nausea

Diagnosis

Sometimes NETs go undiagnosed for many years before they are found. The following tests are used to make a clear diagnosis:

  • Blood/urine tests: Blood and urine tests are conducted to check for abnormal levels of hormones, tumor markers, or genetic traits based on a detailed medical history and physical examination.
  • Imaging tests: Imaging tests are performed to look for tumors and measure their size. Some are used to monitor how well treatment works.
    • Computed tomography (CT or CAT) scan with dye
    • Magnetic resonance imaging (MRI) with dye
    • Positron emission tomography (PET) or PET-CT scan
  • Biopsy: When a biopsy is performed, a small sample of tissue is removed so a pathologist can see if and what cancer cells are present. Molecular testing may be done to find specific genes, proteins, and other factors.

Staging

Staging defines the extent that the tumor has spread. It takes into account the tumor’s size, location, and whether or not it has spread to a lymph node or other organ. This information is used to direct your treatment.

NETs may be local (in one spot), regional (in an area), or metastatic (spread through the body):

  • Early stage (local disease): Often treated with surgery.
  • Metastatic (extensive disease): Treatment might involve hormonal therapy, chemotherapy, targeted therapy, and radiation.

There is a formal staging system for neuroendocrine tumors based on where tumors are found:

  • Stomach
  • Duodenum
  • Ampulla
  • Jejunum
  • Ileum
  • Colon/rectum
  • Pancreas
  • Appendix

Treatments & Side Effects

Your treatment plan is based on:

  • Your diagnosis (stage, grade, location of primary tumor)
  • Your general health
  • Symptoms
  • Practical matters

Your doctor will consider whether or not the tumor(s) can be stopped.

Often, surgery is considered for early-stage disease. Hormone therapy, radiation therapy, chemotherapy, immunotherapy, or targeted therapies are some of the non-surgical options, especially in patients with extensive or metastatic disease.

With timely and appropriate treatment, people with NETs can often live long, productive lives.

​​​​​Surgery

Surgery is done to remove all tumors and nearby lymph nodes. If surgery is not enough or not possible, there are other options. If the cancer has spread to other organs, surgery can be done to prevent symptoms, like bowel obstruction.

​​​​Ablative Therapies

These treatments use thermal heat, cold, or radiation to destroy tumor tissue or block the blood supply to a tumor. They can decrease the tumor’s size, reduce symptoms, and/or slow the growth of a tumor.

Hormone Therapy

​​​​​The hormone somatostatin analog is used to control carcinoid syndrome. Somatostatin regulates the endocrine system and can slow the release of other hormones. It can stop symptoms like flushing and diarrhea.

Learn about hormone therapy

​​​​​Radiation Therapy

Radiation is delivered in a unique way in NET patients. The technique is called PRRT. A somatostatin analog is tagged with a radiation-producing element like Lutetium-177. This drug is injected into the patient via IV. The drug travels in blood and settles down on neuroendocrine tumors cells. Radiation from the drug then damages the DNA of cancer cells in NETs. This treatment can stabilize cancer for a long time.

Learn about radiation therapy

Chemotherapy​​​​​

Chemotherapy drugs travel through the blood to kill cancer cells anywhere in the body. Generally, chemotherapy is only used for NETs that have or will spread to other organs; cause severe symptoms; or don’t respond to other treatments.

Learn about chemotherapy

​​​​​​Chemoembolization

For liver metastases, this is a way to cut the tumor’s blood supply and bring high doses of chemotherapy directly to the liver through a catheter.

​​​​​​This treatment is for people with advanced NETs. It targets a specific gene, protein, pathway, or other factor found in the cancer cell. There are many types, such as VEGF inhibitors that can stop the way tumors grow; or mTOR inhibitors that can activate cell death. Some targeted therapies are only available through a clinical trial.

Learn about targeted therapy

Immunotherapies​​​​​

These treatments, like Interferons, are designed to boost your body’s immune response. These drugs can help the body find and attack NET cells. Some immunotherapies, like immune checkpoint inhibitors, are only available through a clinical trial.

Learn about immunotherapy

Clinical Trials

Clinical trials are studies to find new treatments. Ask your doctor if they would recommend a clinical trial for your treatment. There are many clinical trials studying new ways to treat NETs.

Learn about clinical trials

Treatments to Manage Syndromes

Treatments to manage symptoms from carcinoid syndrome:

  • Somatostatin analogues (SSAs): to prevent, control, or reduce hormone-related symptoms like skin flushing and diarrhea
  • Telotristat (Xermelo®): for carcinoid diarrhea not controlled by an SSA alone
  • Cyproheptadin: to relieve allergy symptoms
  • H1 antagonists: to relieve allergy symptoms
  • Interferons (a type of immunotherapy): to stop or slow tumor growth
  • Hepatic artery embolization (sometimes with chemotherapy): to shrink tumors in the liver
  • Radiofrequency ablation or electroporation: to remove tumors
  • Carcinoid Heart Disease: Long-term elevation of serotonin hormone produced by carcinoid tumors can cause heart problems. You may feel tired, short of breath and have swollen ankles. You should see a cardiologist for your care. Patients with serious carcinoid heart disease may use somatostatin analogues (such as octreotide) or need heart surgery (valve replacement).

Treatments to manage Zollinger-Ellison syndrome:

  • Proton Pump Inhibitors (PPIs): to control gastric acid from GI-Nets
  • Diazoxide: to reduce the effects of insulin secretion

 

Side Effects & Recovery from NET Treatments

Ask your healthcare team, up front, about side effects. You can work together to limit problems. It will be important for you to speak up and ask questions along the way.

Nutrition counseling, relaxation techniques, emotional support, and physical therapy can help speed your recovery and improve your overall well-being.

Surgical side effects: Since surgery can lead to bleeding or infection during recovery, take the time you need to recover well. Ask about steps to avoid infection.

Non-surgical side effects: Drug therapies can cause fatigue, upset stomach, nausea, low blood counts, diarrhea, hair loss, and skin reactions. There are medications for many of these issues. They tend to go away after the treatment period ends.

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