Definition and Epidemiology
Neuroendocrine tumors (NETs) are a rare type of tumor that grows in the neuroendocrine system of the body. When NETs grow in the gastrointestinal tract (GI tract), they are referred to as GI neuroendocrine tumors (GINETs). These tumors are also known as Carcinoids. NETs coming from the neuroendocrine part of the pancreas are also known as pancreatic NETs (PNETs). PNETs differ from the pancreatic adenocarcinoma as they have different biology, natural history, management and prognosis.
Annual incidence of NETs has been increasing worldwide. According to the National Cancer Institute’s SEER cancer registry database, it was estimated to be ~ 8 per 100,000 persons in 2013 and projected to reach ~10-12 per 100,000 in 2023.
The GI tract is actually the most common place for neuroendocrine tumors to develop and GINETs or Carcinoids are the most common tumors of the small bowel.
Biology of NETs
Neuroendocrine cells are a group of hormone-producing cells. There are at least 13 distinct gut neuroendocrine cells all of which may develop NETs and may overproduce various hormones also known as bioactive peptides or amines (insulin, gastrin, somatostatin, vaso active intestinal peptide etc.,).
Approximately 85% of NETs are sporadic (do not run in the family) the remainder occur as part of familial cancer syndromes such as multiple endocrine neoplasia type1 (MEN1), von Hippel-Lindau disease (VHL), von Recklinghausen’s disease (neurofibromatosis 1, NF1), and Tuberous sclerosis (TS).
Classification of NETs
NETs are graded based on how fast-growing they are. Tumor grades for NETs are as follows:
- Grade 1: low divide rate
- Grade 2: faster rate
- Grade 3: high rate of division
NETs are generally grouped into functioning (hormone overproducing) and non functioning (do not produce hormones; clinically “silent”). The majority (60–90%) are clinically nonfunctioning, well-differentiated, slow-growing, found incidentally during unrelated procedures or diagnostic tests. Due to this insidious behavior, many patients present with advanced disease at diagnosis, with regional or distant metastasis observed in up to 80% of patients.
How are NETs diagnosed?
There are a variety of ways that your doctor may test for NETs. When it comes to diagnosing cancer, a biopsy is the most definitive test. A biopsy involves taking a small sample of tissue from an area of the body to determine if it is a cancerous tumor. Your doctor will probably also do additional testing, such as imaging tests to check if the cancer has spread to other parts of the body.
Some common testing methods for GI neuroendocrine disorders include:
- Physical exam. Your doctor will evaluate your physical health and health history to determine any risk factors or symptoms you may have that could be linked to an NET. They may also want to feel for a palpable lump in your abdomen or surrounding area.
- Hormone test. Because NETs can cause an inappropriate release of certain hormones, your doctor may test your blood to look at hormone levels that may indicate an NET.
- CT. A CT scan is a way for your doctor to look at a specific area of the body where a tumor may exist. This imaging scan takes a series of X-ray images to create images of the organs and other places inside of the body.
- MRI. MRIs are another type of imaging scan that uses magnetic fields to take detailed images of the inside of the body. An MRI can be used to evaluate the size and location of a tumor.
- Ga-68 DOTATATE PET/CT. A recently developed and increasingly used diagnostic technique highly specific and sensitive to discovering NETs
- Endoscopic ultrasonography (EUS). Mostly used for the diagnosis of PNETs
- Biopsy. Biopsies involve taking a small tissue sample and sending it to a lab to be examined by a pathologist. Your doctor will need to take a tissue sample from the tumor itself using a long needle device.
GI tract NETs rarely cause any symptoms in the early stages. This type of tumor is usually discovered by accident when a patient gets an imaging scan or surgery related to another issue. In some cases, NETs will cause tumor-related symptoms such as:
- Abdominal pain
- Intestinal bleeding
- Unexplained weight loss
Hormone-related symptoms that can occur from an NET include:
- Skin rash
- Excessive urination
- Flushing of the skin
How are NETs treated?
There are a variety of different treatment options for NETs that depend on the stage and severity of the tumor. Common treatment options include:
Surgery for NET involves the removal of the tumor and any surrounding tissue that may be affected. The removal of the tumor in its entirety is the standard approach to treating GINETs and PNETs. There are a variety of different surgical approaches to removing a NET. Your surgeon will talk to you about different surgery options, depending on the location and size of the tumor.
There are a number of different medications other than chemotherapy drugs that can be used to help destroy cancer cells. Some common medications for NETs include somatostatin analogs (octreotide or lanreotide), targeted therapy, and immunotherapy.
Peptide receptor radionuclide therapy
Peptide receptor radionuclide therapy or PRRT is a type of radioactive drug that can help eliminate cancer cells by binding to the cell receptors and using radiation to destroy them. This type of therapy is fairly new, gaining FDA approval in 2018.
Chemotherapy can be used to treat NETs that have spread to new areas of the body or are causing severe symptoms. Your oncologist will develop a chemotherapy regimen that involves multiple doses of different chemotherapy drugs given over time.
Radiation uses high-energy particles to destroy cancer cells. GINETs are commonly treated with a type of radiation called external beam radiation. This type of therapy is usually used as a supportive method for patients with advanced cancer that has spread to the bones.
A GI neuroendocrine disorder is a rare and confusing diagnosis. Your doctor can work with you to help educate you and guide you through the treatment process. The UCF Health Endocrinology team is here to help any patients who have concerns about a potential GI neuroendocrine disorder. Our general practice and holistic physicians can help you maintain your health with a preventative approach. Schedule your visit today. (Insert link to request appt with Dr. Neychev)