GEP-NETs are sometimes called carcinoid tumors or islet cell tumors. They typically develop in neuroendocrine cells, which produce hormones. GEP-NETs can be cancerous (malignant) or noncancerous (benign). They’re usually slow-growing, taking many years to form, and may not cause symptoms until they’ve spread to other parts of the body. (1,2) A functional GEP-NET is one that secretes extra hormones. Some types include:
Carcinoid These tumors secrete abnormal levels of serotonin, a hormone that helps regulate mood and multiple other bodily functions. They can cause a condition called carcinoid syndrome.Gastrinoma These tumors form in the cells that make gastrin, a hormone that aids digestion. The result can be Zollinger-Ellison syndrome, characterized by excess stomach acid, stomach ulcers, and diarrhea.Insulinoma These tumors develop in the cells that make insulin, a hormone that regulates blood sugar.Glucagonoma These tumors begin in the cells that make glucagon, a hormone that increases blood-sugar levels.VIPomas These tumors overproduce a substance called vasoactive intestinal peptide, resulting in Verner-Morrison syndrome.Somatostatinomas These tumors raise levels of somatostatin, a hormone that suppresses the secretion of other hormones. (3,4)
Nonfunctional Tumor Symptoms
Common symptoms of a nonfunctional GEP-NET include:
DiarrheaIndigestionLump in the abdomenPain in the abdomen or backJaundice — yellowing of the skin or whites of the eyes (3)
Functional Tumor Symptoms
Symptoms of a functional GEP-NET can vary, depending on the kind of hormones the tumor produces. Abnormally high levels of serotonin can cause:
FlushingWheezingDiarrheaSkin lesionsValvular heart disease — damage or a defect in one of the four heart valves (5)
Too much gastrin can cause:
Stomach ulcersAbdominal pain that may spread to the backGastroesophageal reflux disease (GERD)Diarrhea
Excessive insulin can cause:
Low blood sugar levels, which can trigger blurred vision, headaches, light-headedness, irritability, sweating, confusion, hunger, shakiness, or weaknessA fast heartbeat
Too much glucagon can cause:
A rash on the face, stomach, or legsHigh blood sugar levels, which can lead to headaches, frequent urination, dry skin and mouth, hunger, thirst, tiredness, or weaknessUnexplained weight lossDiarrheaBlood clotsA sore tongue or sores in the corners of the mouth
Abnormally high amounts of vasoactive intestinal peptide can cause:
Watery diarrheaDehydration, which is marked by thirst, dizziness, headaches, dry skin and mouth, tiredness, and infrequent urinationLow potassium levels in the blood, which can cause muscle weakness, achiness, cramps, numbness, tingling, frequent urination, fast heartbeat, confusion, or thirstAbdominal pain or crampsUnexplained weight loss
An excess of somatostatin can cause:
High blood sugarDiarrheaGallstonesSteatorrhea (foul-smelling stool that floats)JaundiceUnexplained weight loss (3)
While GEP-NETs are considered rare, incidence appears to be on the rise. Data from the U.S. Surveillance Epidemiology and End Results published in the journal Annals of Gastroenterology showed an increase of more than 400 percent from 1973 to 2004. (4) These tumors can occur in people of any age but are more likely to develop in individuals older than 50. They are slightly more common in men than in women. (6)
Physical Exam The doctor checks for any physical signs of the disease and also asks about the patient’s health and family history.Chromogranin A Test Higher than normal levels of chromogranin A in the blood, along with normal levels of hormones like gastrin, glucagon, and insulin, can be a sign of a GEP-NET.Abdominal Computerized Tomography (CT) Scan This imaging test uses X-rays to create detailed pictures of the abdomen, revealing tumors.Magnetic Resonance Imaging (MRI) This test uses a magnet, radio waves, and a computer to create images.Positron Emission Tomography (PET) A PET scan is an imaging test that uses radioactive tracers to reveal how tissues and organs are functioning.Laparotomy A laparotomy is a type of surgery done through an incision in the wall of the abdomen. This is typically performed in order to biopsy or remove a tumor.Biopsy A biopsy is a procedure to remove small pieces of tissue to view under a microscope and check for cancer. There are many ways to perform a biopsy. The doctor might insert a needle while using an X-ray or ultrasound for guidance. Or a surgeon might remove tissue while performing another procedure, such as a laparotomy.Somatostatin Receptor Scintigraphy This scan looks for small GEP-NETs. First doctors inject radioactive octreotide (a hormone that attaches to tumors) into a vein. A special camera detects radioactivity to pinpoint tumor location.Endoscopic Ultrasound Doctors insert an endoscope — a slim, tube-like instrument with a light and lens for viewing — into the body via the mouth or rectum.Endoscopic Retrograde Cholangiopancreatography (ERCP) This procedure lets doctors see if a tumor is blocking bile ducts (tubes that carry bile). Physicians insert an endoscope via the mouth through the digestive system and into the small intestine, then insert a catheter through the endoscope into the ducts. Doctors inject a special dye and take an X-ray. If the duct is blocked, doctors may insert a stent to keep it open.Bone Scan To check for cancer cells in the bone, doctors inject a small amount of radioactive material into the veins. This substance collects in bones with cancer, which doctors can see with a scanner.Scope Procedures Doctors insert scopes to see different areas inside the body and detect GEP-NETs. These procedures include colonoscopy and panendoscopy. (3,4,6)
There are several different staging systems used for GEP-NETs, which classify the tumors using a complex set of criteria. The World Health Organization (WHO) promotes a system that divides tumors into the following categories:
NET G1 These tumors are the least aggressive and are considered “well-differentiated” and low-grade, with a Ki-67 index of 2 percent or less. (The Ki-67 index is a measure of the proportion of cells that are nearly ready to begin splitting — hence, it’s a measure of how fast a tumor is growing.)NET G2 These are considered “well-differentiated” and intermediate-grade, with a Ki-67 index between 3 and 20 percent.NEC G3 These are “poorly-differentiated” tumors and are considered high-grade, with a Ki-67 index of more than 20 percent. These tumors often grow and spread rapidly. (7,8)
The European Neuroendocrine Tumor Society also has a staging system based on the “tumor-node-metastasis” (TNM) scale. (4) In this system:
T Stands for Tumor Doctors evaluate the size and extent of the tumor.N Stands for Node Tests assess whether tumor cells have spread to nearby lymph nodes.M Stands for Metastasis Physicians evaluate whether the tumor has metastasized, or spread, to distant areas of the body.
Typically, numbers or letters appear after the T, N, and M. They provide more details about the tumor, with higher numbers indicating that the cancer is more advanced. (7,8) These staging systems are technical and confusing; a doctor can explain what they mean in more detail.
To remove the tumorTo stop or slow the growth and spread of the tumorTo relieve symptoms associated with too much hormone production (4)
Surgery
Surgery to remove the GEP-NET is the preferred treatment. The type of surgery depends on where the tumor is located and how big and aggressive it is. Sometimes doctors need to remove nearby organs as well. (5) If the cancer has spread, doctors might still be able to perform surgery or recommend other procedures to relieve symptoms. These may include:
Radiofrequency Ablation A special probe with small electrodes kills cancer cells.Cryoablation Tissue is frozen to destroy cancer cells.Tumor Debulking Surgeons remove parts of the tumor that are producing too many hormones.Hepatic Artery Embolization Doctors inject a contrast dye and small particles into the hepatic artery (the major vessel that delivers blood to the liver) to stop its blood supply from reaching the tumor. (9)Chemoembolization Doctors inject chemotherapy medicine into the hepatic artery during a hepatic artery embolization procedure. (3,5,6,9)
A small number of people with GEP-NETs might be candidates for a liver transplant, although studies have shown that patients who have a transplant face a high risk of tumor recurrence. (4)
Drug Treatment
Some medicines have been shown to slow GEP-NETs. Options include:
Somatostatin Analogs The drugs octreotide (Sandostatin LAR Depot) and lanreotide (Somatuline Depot) can improve symptoms caused by some types of functional GEP-NETs. They may also stabilize tumor growth. (4) These medicines are typically options for tumors that can’t be surgically removed, according to an article published in the journal Clinical Advances in Hematology & Oncology. (10)Targeted Therapies For people with GEP-NETs that affect the pancreas, the targeted drugs everolimus (Afinitor) and sunitinib (Sutent) have been shown to slow tumor growth and improve survival. (3,11)Targeted Radiation Drug Lutetium Lu 177 dotatate (Lutathera) binds to a specific molecule, called a somatostatin receptor, found on certain tumors; then it delivers a dose of radiation to the tumor. In clinical trials, the drug reduced the risk of disease progression or death by 79 percent. (2)Chemotherapy Chemotherapy uses medicines to kill cancer cells. Among the many chemo drugs used to treat GEP-NETs are streptozocin (Zanosar), doxorubicin (Adriamycin), etoposide (Toposar, VePesid), dacarbazine (DTIC-Dome), fluorouracil (Adrucil), and cisplatin (Platinol). Some of these drugs are given in combination. (4,5)Interferon Alpha This therapy, given as an injection, has been used since the early 1980s to treat GEP-NETs. It can cause side effects such as flu-like symptoms, thyroid disorders, chronic fatigue syndrome, and low blood counts. Interferon alpha is often used in combination with other treatments. (4)
Supportive Care
Sometimes GEP-NETs are so advanced that there aren’t any good treatment options. Doctors might recommend supportive care to relieve symptoms or to help alleviate the side effects of treatment. Some examples of supportive care may include medicines to help counter:
Stomach ulcersDiarrheaHigh or low blood sugar (3)
Clinical Trials
Anyone with a GEP-NET might want to consider enrolling in a clinical trial. These studies give patients the opportunity to receive a novel medicine not available to the general public, which may also lead the way to improved treatments in the future. You can search for a clinical trial on the National Cancer Institute’s website or by visiting ClinicalTrials.gov. (3) When diagnosed, between 65 and 95 percent of GEP-NETs have already spread to distant areas of the body, such as the liver, noted researchers in the Journal of the Pancreas. (12) Metastatic disease is harder to treat. Studies have shown that people with “well- and moderately-differentiated distant metastases” have a five-year survival probability of 35 percent. Those with “poorly-differentiated distant metastases” have a five-year survival probability of only about 4 percent. (4) It’s important to remember that every cancer case is different, and survival statistics are only averages — not to mention they’re based on data that is older than some of the therapies now in use. Talking to a doctor is key to understanding each person’s unique situation. The International Neuroendocrine Cancer Alliance offers useful information about neuroendocrine tumors. The organization can also link patients with local support groups. It’s important to maintain healthy habits throughout treatment: to eat well, exercise regularly, and get enough sleep. Reaching out to others for emotional support or help with everyday tasks can also help enormously. (13)
