title: Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression.
abstract: OBJECTIVE
  Knowledge of clinical course of pancreatic endocrine carcinomas (PECs) is poor. This study aimed to determine the time to progression of advanced PECs, and to identify predictors capable of selecting subgroups with higher risk of progression.
  
  
  METHODS
  In this multicenter retrospective analysis, patients with advanced PECs were enrolled. Staging was according to European Neuroendocrine Tumors Society guidelines. Grading was based on proliferation index using Ki67 immunohistochemistry. The primary end point was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The Cox regression proportional hazard model was used to identify predictors for tumor progression.
  
  
  RESULTS
  Two hundred two patients with PECs were enrolled, including 172 with well-differentiated and 30 with poorly differentiated endocrine carcinomas. There were 34 patients with stage III and 168 with stage IV tumors. G1 tumors were present in 19.7% of patients, whereas 60.1% of patients had G2 tumors, and the remaining 20.2% had G3 tumors. Disease progression occurred in 166 patients (82.2%), at a median interval of 10 months (interquartile range, 5 to 22) from diagnosis. Median PFS was 14 months. Different PFS were observed depending on G grade (P < .001) and tumor differentiation (P < .001) and in patients who did not receive any antitumor treatment (P = .002). The major risk factor for progression was the proliferation index Ki67 (hazard ratio, 1.02 for each increasing unit; P < .001). Overall 5-year survival was 44.1%.
  
  
  CONCLUSIONS
  The vast majority of patients with advanced PECs undergo disease progression. The major risk factor for progression is Ki67 index, which should lead physicians dealing with PECs to plan appropriate follow-up programs and therapeutic strategies.
authors.affiliation: II School of Medicine, Sapienza University of Roma, Sant'Andrea Hospital, Via di Grottarossa 1035, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Panzuto
authors.forename: Letizia
authors.initials: L
authors.lastname: Boninsegna
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.forename: Davide
authors.initials: D
authors.lastname: Campana
authors.forename: Maria
authors.initials: M
authors.lastname: Pia Brizzi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Capurso
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.forename: Luigi
authors.initials: L
authors.lastname: Dogliotti
authors.forename: Paola
authors.initials: P
authors.lastname: Tomassetti
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
mesh_terms: D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D019394:Ki-67 Antigen