title: Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE).
abstract: BACKGROUND
  Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival.
  
  
  METHODS
  From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses.
  
  
  RESULTS
  Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome.
  
  
  CONCLUSIONS
  Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.
authors.affiliation: Department of Surgery, University Hospital La Princesa, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martin-Perez
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.forename: Paula
authors.initials: P
authors.lastname: Jimenez-Fonseca
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
authors.forename: Adolfo
authors.initials: A
authors.lastname: Beguiristain-Gomez
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso-Orduña
authors.forename: Purificacion
authors.initials: P
authors.lastname: Martinez Del Prado
authors.forename: Carles
authors.initials: C
authors.lastname: Villabona-Artero
authors.forename: Jose A
authors.initials: JA
authors.lastname: Diaz-Perez
authors.forename: Antonio
authors.initials: A
authors.lastname: Monleon
authors.forename: Monica
authors.initials: M
authors.lastname: Marazuela
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pachon
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre-Valera
authors.forename: Isabel
authors.initials: I
authors.lastname: Sevilla
authors.forename: Angel
authors.initials: A
authors.lastname: Castaño
authors.forename: Rocio
authors.initials: R
authors.lastname: Garcia-Carbonero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012042:Registries / Q000706:statistics & numerical data; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen