Neuroendocrine tumors develop from hormone-producing cells that are located in the lining of body cavities. These cells (and their tumors) can be found in the lung (bronchopulmonary “carcinoid”), stomach (gastric “carcinoid”), pancreas (“pancreatic or islet cell carcinoma”, insulinomas, glucagonomas, somatostatinomas, gastrinomas, VIPomas), intestines (“carcinoid”), appendix (appendiceal “carcinoid”) and rectum (rectal “carcinoid”). Tumors mostly develop in the gut – about 60% - and the lungs – about 30%. Tumors can also develop in rarer sites like the gall bladder, thymus, breast and ovary. They can metastasize to all sites of the body but principally to the liver. Overall, neuroendocrine tumors comprise between 1-2% of all cancers and they have increasingly been identified. It is estimated that 10,000-15,000 new cases of “carcinoid” will be diagnosed every year.

Risk Factors

Increasing incidence of NETs (from Modlin et al. Lancet Oncology 2008)

The risk factors that relate to the development of neuroendocrine tumors are not well known. A family history of the multiple endocrine neoplasia type I (MEN1) is associated with an increased risk of some types of pancreatic tumors. This is an extremely rare genetic disorder and is also related to tumors of the stomach as well as to the parathyroid and pituitary. More recently, there is increasing evidence for a family link for neuroendocrine tumors at other sites, for example, the small intestine. It is also well known that certain bowel diseases like celiac disease and inflammatory bowel disease (Crohn's disease and ulcerative colitis) have an increased risk of developing neuroendocrine tumors. There is also evidence that conditions that affect the stomach’s ability to produce acid may also increase the risk. In general, neuroendocrine tumors present a considerable diagnostic and therapeutic challenge as their clinical presentation is usually nonspecific, for example, a cough and shortness of breath (lung), high blood sugar (pancreas), diarrhea (pancreas, intestine), flushing (lung, intestine) or they may have no symptoms. They are also usually diagnosed at a late, when metastases are already evident. The mean age of diagnosis is about 60 years, but these tumors may begin developing 10-15 years before this.

The tumors can be identified using a range of imaging approaches including CAT scan, MRI (magnetic resonance imaging), somatostatin receptor scintigraphy (Octreoscan), whole-body positron emission tomography (PET) or endoscopy/ultrasound. Bronchoscopy is used for the lungs. These have a range of sensitivities (20-95%) and are dependent on the size of the tumor. Smaller cancers less than 0.5 cm are difficult to detect and metastases, that develop in the liver, require to be a certain size before they can be detected.

No curative treatment exists for neuroendocrine tumors except for radical surgery (total removal of the tumor and adjacent tissue). Other types of treatment include surgical debulking (removal of as much tumor as possible), tumor embolization (killing tumor cells with heat or cold), biological therapy (treatment with somatostatin analogs like octreotide, lanreotide or pasireotide, tyrosine kinase receptor inhibitors like sutent and mTOR inhibitors like everolimus), chemotherapy (only very aggressive tumors – those with high Ki67 levels) and radiotherapy like peptide radio-receptor therapy (PRRT). Different tumors have different sensitivities to drugs and therapy effectiveness ranges between 0-60%. The most effective therapies treat the symptoms and lengthen the time period before a relapse or recurrence. The latter usually by 6 months to two years. There are no current ways to determine how a patient will respond to a therapy except that somatostatin receptors need to be identified for somatostatin therapies to work and tumors with a low Ki67 will not respond to chemotherapy.

After treatment, a tumor can be in “remission” and is not detected in the body using current imaging. Usually there are no symptoms. This can be temporary or permanent. Neuroendocrine tumors usually recur after the original treatment. Patients often realize that they have to “live” with a chronic disease. They also realize the importance of accurate monitoring and testing.

Neuroendocrine Disease Testing:
Molecular Diagnostics

With, recurrence comes the cycle of testing which is undertaken to learn as much as possible about how the disease is progressing. One method of testing is provided by the NETest. This blood-based test is non-invasive, and in addition to assessing disease progress can also be used to evaluate whether a treatment is working. Both of these features are advantageous to both the patient and the physician. Treatment plans can be modified accordingly and appropriately and peace of mind may be achieved.