title: Will clinical heterogeneity of neuroendocrine tumors impact their management in the future? Lessons from recent trials.
abstract: Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms arising from the diffuse neuroendocrine system. In the last few years, advances in our understanding of the biology of these tumors have translated into an expansion of treatment options for patients with NETs. Current treatment modalities include somatostatin analogs (SSAs), radiolabeled SSAs, targeted agents, cytotoxic drugs and liver-directed therapies for the management of metastatic disease.
  
  
  
  Recent studies have expanded the role of SSAs in gastroenteropancreatic (GEP)-NETs, and everolimus has shown robust antitumor activity across a broad range of NETs of the lung and GEP tract. The radiolobeled SSA Lu-DOTATATE has been investigated in a randomized phase III trial, and has demonstrated exceptional efficacy and tolerability in patients with progressive midgut NETs. The new serotonin inhibitor telotristat etiprate has shown significant activity in the palliation of symptoms of carcinoid syndrome, and its approval by regulatory authorities is expected soon.
  
  
  
  The field of NETs has been transformed from one dominated by limited treatment options to one characterized by an increasing number of therapeutic agents and active clinical trials. Navigating the current therapeutic algorithm may be challenging, and requires an understanding both of the heterogeneity of NETs and of characteristics that are shared by NETs across tumor subtypes.
authors.affiliation: Department of GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cives
authors.forename: Heloisa P
authors.initials: HP
authors.lastname: Soares
authors.forename: Jonathan
authors.initials: J
authors.lastname: Strosberg
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007414:Intestinal Neoplasms / Q000628:therapy*; D008187:Lutetium / Q000627:therapeutic use; D018358:Neuroendocrine Tumors / Q000473:pathology / Q000628:therapy*; D015282:Octreotide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000628:therapy*
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013004:Somatostatin; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide