Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasing in incidence, but delay in diagnosis is common. Patients may present with specific symptoms related to a functional tumor or vague gastrointestinal symptoms, emphasizing the importance of maintaining a high index of suspicion for this disease.
The majority of GEP-NETs arise sporadically. Multiple endocrine neoplasia type 1 is the most common inherited syndrome in which nonfunctional pancreatic neuroendocrine tumors (PNETs) predominate.
68Ga tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate (68Ga-DOTATATE) has excellent sensitivity and specificity for GEP-NETs. It is used to detect the location of unknown primary tumors and to assess for distant disease. It is not used for routine surveillance.
Surgical resection is the standard of care for localized GEP-NETs. In advanced disease, surgery may be appropriate when R0 resection can be achieved, or cytoreduction is performed for palliation of symptoms.
In cases in which hepatic metastases are unresectable, hepatic arterial embolotherapies may be used. Peptide receptor radionuclide therapy is efficacious for hepatic and extrahepatic metastases.
Systemic therapy for advanced extrapancreatic NETs includes somatostatin analogues and the targeted therapy everolimus. In PNETs, FAS (5-fluorouracil, doxorubicin, and streptozocin), capecitabine and temozolomide, and sunitinib are additional options.
Neuroendocrine tumors (NETs) originate from enterochromaffin cells of the diffuse endocrine system. A diverse set of tumors, they most commonly arise from the gastrointestinal (GI) tract, pancreas, lungs, and bronchi. Less common sites include the thyroid, parathyroid, pituitary gland, adrenal glands, and thymus. This chapter focuses on the low- and intermediate-grade gastroenteropancreatic NETs (GEP-NETs) and lung NETs, leaving small cell carcinomas, medullary thyroid cancer, neuroblastoma, and Merkel cell carcinomas (all technically neuroendocrine neoplasms) to other chapters in this text.
NETs may secrete peptides and neuroamines that cause specific clinical symptoms, although this is not universally present even among tumors originating from the same anatomic site. Localized disease is treated surgically for curative intent. Locoregional or metastatic disease not amenable to surgical resection can be managed with somatostatin analogues (SSAs), peptide receptor radionuclide therapy (PRRT), liver-directed therapy, cytotoxic chemotherapy, or targeted therapies. This chapter discusses current diagnostic and management strategies for lung and GEP-NETs.
EPIDEMIOLOGY AND RISK ASSESSMENT
The Surveillance Epidemiology End Results (SEER) database has catalogued a 6.4-fold increase in the incidence of NETs from 1973 to 2012. This increase was consistent across anatomic site, grade, and stage. Globally, NETs remain relatively rare with an age-adjusted incidence of 6.98 per 100,000 individuals.1 The disease is slightly more common in women (52.7%) and those 65 years old or older (25.3 per 100,000 persons). Among GEP-NETs, the most common site of origin is the small intestine followed by the rectum and pancreas.1
The cause of the increased incidence is unknown but often attributed to greater disease awareness and improved diagnostic capabilities. Common behavioral risk factors such as smoking, obesity, and excessive alcohol use do not appear to play a role in the ...