Several issues help define appropriate treatment of a<unk> , including its location, invasiveness, hormone secretion, and metastasis. Treatments may be aimed at curing the disease or at relieving symptoms (palliation). Observation may be feasible for non-functioning low-grade<unk> s. If the tumor is locally advanced or has metastasized, but is nonetheless slowly growing, treatment that relieves symptoms may often be preferred over immediate challenging surgeries. Intermediate and high grade tumors (noncarcinoids) are usually best treated by various early interventions (active therapy) rather than observation (wait-and-see approach). Treatments have improved over the past several decades, and outcomes are improving. In malignant carcinoid tumors with carcinoid syndrome, the median survival has improved from two years to more than eight years. Detailed guidelines for managing<unk> s are available from ESMO, NCCN and a UK panel. The NCI has guidelines for several categories of<unk> : islet cell tumors of the pancreas, gastrointestinal carcinoids, Merkel cell tumors and pheochromocytoma/paraganglioma. However, effective predictive biomarkers are yet to be discovered. Similarly, recent advances in understanding<unk> 's molecular and genomic alterations still have to find their ways into a definitive management strategy. Surgery Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in<unk>  cancers for palliation of symptoms and possibly increased lifespan. Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs. Symptomatic relief In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs. These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic<unk>  MIDgut tumors): at least in this subset of<unk> s, average tumor stabilization was 14.3 months compared to 6 months for placebo. The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic<unk> s) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty-five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47. Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS. Other medications that block particular secretory effects can sometimes relieve symptoms. Chemotherapy Interferon is sometimes used to treat GEP-NETs. Its effectiveness is somewhat uncertain, but low doses can be titrated within each person, often considering the effect on the blood leukocyte count; Interferon is often used in combination with other agents, especially somatostatin analogs such as octreotide. Gastrointestinal<unk> s Most gastrointestinal carcinoid tumors tend not to respond to chemotherapy agents, showing 10 to 20% response rates that are typically less than 6 months. Combining chemotherapy medications has not usually been of significant improvement showing 25 to 35% response rates that are typically less than 9 months. The exceptions are poorly differentiated (high-grade or anaplastic) metastatic disease, where cisplatin with etoposide may be used and Somatostatin Receptor Scintigraphy (SSRS) negative tumors which had a response rate in excess of 70% compared to 10% in strongly positive SRSS carcinoid tumors. PanNETs Targeted therapy with everolimus (Afinitor) and sunitinib (Sutent) is approved by the FDA in unresectable, locally advanced or metastatic PanNETs. Some PanNETs are more responsive to chemotherapy than gastroenteric carcinoid tumors. Several agents have shown activity and combining several medicines, particularly doxorubicin with streptozocin and fluorouracil (5-FU or f5U), is often more effective. Although marginally effective in well-differentiated PETs, cisplatin with etoposide is active in poorly differentiated<unk>  cancers (PDNECs). Radionuclide therapy Peptide receptor radionuclide therapy (PRRT) is a type of radioisotope therapy (RIT) in which a peptide or hormone conjugated to a radionuclide or radioligand is given intravenously, the peptide or neuroamine hormone previously having shown good uptake of a tracer dose, using Somatostatin receptor imaging as detailed above. This type of radiotherapy is a systemic therapy and will impact somatostatin positive disease. The peptide receptor may be bound to lutetium-177, yttrium-90, indium-111 and other isotopes including alpha emitters. This is a highly targeted and effective therapy with minimal side effects in tumors with high levels of somatostatin cell surface expression, because the radiation is absorbed at the sites of the tumor, or excreted in the urine. The radioactively labelled hormones enter the tumor cells which, together with nearby cells, are damaged by the attached radiation. Not all cells are immediately killed; cell death can go on for up to two years. PRRT was initially used for low grade<unk> s. It is also very useful in more aggressive<unk> s such as Grade 2 and 3<unk> s provided they demonstrate high uptake on SSTR imaging to suggest benefit. Hepatic artery Metastases to the liver can be treated by several types of hepatic artery treatments based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70–80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked. * Hepatic artery embolization (HAE) occludes the blood flow to the tumors, achieving significant tumor shrinkage in over 80%. In hepatic artery chemotherapy, the chemotherapy agents are given into the hepatic artery, often by steady infusion over hours or even days. Compared with systemic chemotherapy, a higher proportion of the chemotherapy agents are (in theory) delivered to the lesions in the liver. * Hepatic artery chemoembolization (HACE), sometimes called transarterial chemoembolization (TACE), combines hepatic artery embolization with hepatic artery chemoinfusion: embospheres bound with chemotherapy agents, injected into the hepatic artery, lodge in downstream capillaries. The spheres not only block blood flow to the lesions, but by halting the chemotherapy agents in the neighborhood of the lesions, they provide much better targeting leverage than chemoinfusion provides. * Selective internal radiation therapy (SIRT) for<unk>  metastases to the liver delivers radioactive microsphere therapy (RMT) by injection into the hepatic artery, lodging (as with HAE and HACE) in downstream capillaries. In contrast to hormone-delivered radiotherapy, the lesions need not overexpress peptide receptors. The mechanical targeting delivers the radiation from the yttrium-labeled microspheres selectively to the tumors without unduly affecting the normal liver. This type of treatment is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, including<unk>  malignancies. Other therapies AdVince, a type of gene therapy using a genetically modified oncolytic adenovirus and supported by the crowdfunding campaign iCancer was used in a Phase 1 trial against<unk>  in 2016. Further efforts towards more personalized therapies in<unk> s are undertaken i.a. combining drug screening platforms and patient-derived ex vivo cell cultures that mimic relevant aspects of the original tumors.
Neuroendocrine tumor
Pituitary adenoma
Metastatic insulinoma
Insulinoma
Glucagonoma
Granular cell tumor
Endocrine gland neoplasm
Glial tumor