title: Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus.
abstract: BACKGROUND
  Everolimus, an oral inhibitor of mammalian target of rapamycin, significantly prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET). Chromogranin A (CgA) and neuron-specific enolase (NSE) are considered general biomarkers of these tumors.
  
  
  OBJECTIVE
  The objective of the study was to evaluate the prognostic value of CgA and NSE in patients with pNET treated with everolimus.
  
  
  METHODS
  Patients with low- to intermediate-grade advanced pNET enrolled in two phase 2 studies [RAD001 in Advanced Neuroendocrine Tumors (RADIANT-1) and single institution phase II study at The University of Texas M. D. Anderson Cancer Center] received everolimus. Blood samples were collected and analyzed by a central laboratory at baseline and monthly thereafter. PFS and overall survival (OS) were evaluated in patients with elevated and nonelevated baseline CgA/NSE levels.
  
  
  RESULTS
  In RADIANT-1, elevated vs. nonelevated baseline CgA was associated with shorter median PFS (8.34 vs. 15.64 months; P = 0.03) and OS (16.95 months vs. not reached; P < 0.001). Elevated vs. nonelevated baseline NSE resulted in shorter median PFS (7.75 vs. 12.29 months; P = 0.01) and OS (13.96 vs. 24.90 months; P = 0.005). Median PFS was prolonged in patients with early CgA or NSE response (11.0 vs. 5.0 months) compared with those without early biomarker response. More patients with CgA (87 vs. 50%) or NSE (81 vs. 14%) response experienced tumor shrinkage compared with those without response. CgA response data from the single-institution phase II study at The University of Texas M. D. Anderson Cancer Center study are consistent with data from the RADIANT-1 study.
  
  
  CONCLUSIONS
  Elevated baseline CgA/NSE provided prognostic information on PFS and survival; early CgA/NSE responses are potential prognostic markers for treatment outcomes in patients with advanced pNET.
authors: Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 426, Houston, Texas 77030, USA. jyao@mdanderson.org
authors: James C
authors: JC
authors: Yao
authors: Marianne
authors: M
authors: Pavel
authors: Alexandria T
authors: AT
authors: Phan
authors: Matthew H
authors: MH
authors: Kulke
authors: Sakina
authors: S
authors: Hoosen
authors: Jessica
authors: J
authors: St Peter
authors: Azzeddine
authors: A
authors: Cherfi
authors: Kjell E
authors: KE
authors: Öberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D053379:Chromogranin A / Q000097:blood*; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011379:Prognosis; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D007166:Immunosuppressive Agents; D000068338:Everolimus; D010751:Phosphopyruvate Hydratase; D020123:Sirolimus