title: Prognostic stratification of metastatic gastroenteropancreatic neuroendocrine neoplasms by 18F-FDG PET: feasibility of a metabolic grading system.
abstract: The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of (18)F-FDG PET in inoperable multifocal disease.
  
  
  METHODS
  Retrospective, dual-center analysis was performed on 89 patients with histologically confirmed, inoperable metastatic gastroenteropancreatic NENs undergoing (18)F-FDG PET/CT within the staging routine. Metabolic (PET-based) grading was in accordance with the most prominent (18)F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum standardized uptake value ≤ 1.0; mG2, 1.0-2.3; mG3, >2.3. Other potential variables influencing overall survival, including age, tumor origin, performance status, tumor burden, plasma chromogranin A (≥600 μg/L), neuron-specific enolase (≥25 μg/L), and classic grading (Ki-67-based) underwent univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), with a P value of less than 0.05 considered significant.
  
  
  RESULTS
  The median follow-up period was 38 mo (95% confidence interval [CI], 27-49 mo); median overall survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21-37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22 (25.0%) mG2, and 57 (64.8%) mG3. On multivariate analysis, markedly elevated plasma neuron-specific enolase (P = 0.016; hazard ratio, 2.9; 95% CI, 1.2-7.0) and high metabolic grade (P = 0.015; hazard ratio, 4.7; 95% CI, 1.2-7.0) were independent predictors of survival.
  
  
  CONCLUSIONS
  This study demonstrated the feasibility of prognostic 3-grade stratification of metastatic gastroenteropancreatic NENs by whole-body molecular imaging using (18)F-FDG PET.
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany samer.ezziddin@ukb.uni-bonn.de.
authors.forename: Samer
authors.initials: S
authors.lastname: Ezziddin
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Adler
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Sabet
authors.affiliation: Department of Nuclear Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Thorsten Dirk
authors.initials: TD
authors.lastname: Pöppel
authors.affiliation: Institute of Pathology, University Hospital Essen, Essen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Grabellus
authors.affiliation: Department of Internal Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Yüce
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.affiliation: Department of Radiology, University Hospital Bonn, Bonn, Germany; and.
authors.forename: Birgit
authors.initials: B
authors.lastname: Simon
authors.affiliation: Institute of Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Höller
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Biersack
authors.affiliation: Department of Nuclear Medicine, University Hospital Essen, Essen, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Nagarajah
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D019394:Ki-67 Antigen; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG; PET/CT; gastroenteropancreatic; neuroendocrine tumors; prognostic stratification; tumor grading