title: Advanced digestive neuroendocrine tumors: metastatic pattern is an independent factor affecting clinical outcome.
abstract: OBJECTIVE
  The objective of this study was to determine the impact of different metastatic spread patterns on outcome in advanced digestive neuroendocrine tumors (NETs).
  
  
  METHODS
  This was a retrospective analysis of patients with stage IV NETs, classified as group 1 (unilobar liver metastases), group 2 (bilobar liver metastases), group 3 (extra-abdominal metastases). End points were overall survival (OS) and progression-free survival (PFS). Risk factor analysis was performed using Cox proportional hazard model.
  
  
  RESULTS
  Of the 229 patients, 135 (58.9%) had pancreatic, and 94 (41.1%) small bowel NETs: 32 (13.9%) were included in group 1, 179 (78.2%) in group 2, and 18 (7.9%) in group 3. Median Ki67 was 4.5%. Overall, 5-year OS was 55%. Different OS was observed among the 3 groups: median survival not reached, 81 and 8 months, respectively (P < 0.001). Median PFS was 18 months. Both OS and PFS were significantly affected by Ki67 and metastatic spread pattern.
  
  
  CONCLUSIONS
  The stratification of stage IV NET patients based on metastatic patterns, alongside Ki67, predicts the clinical outcome. The extent of metastatic disease is a previously unrecognized variable, which should be considered when evaluating the results of treatments in NET patients with advanced disease.
authors: From the *Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome; †Dept of Surgery, Pancreatic Surgery Unit, Università Politecnica delle Marche, Ancona; ‡Ospedale Sacro Cuore Don Calabria, Negrar; §Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna; ∥Radiology, ¶Pathology Unit, and #Surgery 1, Sapienza University of Rome, Sant'Andrea Hospital, Rome; **ARC-NET Center for Applied Research on Cancer and Department of Pathology and Diagnostics, University of Verona, Verona; and ††Medical Oncology, Università Politecnica delle Marche, Ancona, Italy.
authors: Francesco
authors: F
authors: Panzuto
authors: Elettra
authors: E
authors: Merola
authors: Maria
authors: M
authors: Rinzivillo
authors: Stefano
authors: S
authors: Partelli
authors: Davide
authors: D
authors: Campana
authors: Elsa
authors: E
authors: Iannicelli
authors: Emanuela
authors: E
authors: Pilozzi
authors: Paolo
authors: P
authors: Mercantini
authors: Michele
authors: M
authors: Rossi
authors: Gabriele
authors: G
authors: Capurso
authors: Aldo
authors: A
authors: Scarpa
authors: Stefano
authors: S
authors: Cascinu
authors: Paola
authors: P
authors: Tomassetti
authors: Massimo
authors: M
authors: Falconi
authors: Gianfranco
authors: G
authors: Delle Fave
mesh_terms: D000368:Aged; D004067:Digestive System Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D019394:Ki-67 Antigen