title: Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome.
abstract: Several risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far.
  
  
  
  A retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method.
  
  
  
  Two hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively.
  
  
  
  In stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs.The Oncologist2017;22:409-415Implications for Practice:Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.
authors.affiliation: Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Panzuto
authors.affiliation: Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy.
authors.forename: Elettra
authors.initials: E
authors.lastname: Merola
authors.affiliation: Department of Hepatology and Gastroenterology, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany.
authors.forename: Marianne Ellen
authors.initials: ME
authors.lastname: Pavel
authors.affiliation: Department of Gastroenterology, Philipps-University of Marburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rinke
authors.affiliation: Clinical Division of Gastroenterology, Medical University Graz, Austria.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Kump
authors.affiliation: Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Partelli
authors.affiliation: Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Rinzivillo
authors.affiliation: Department of Radiology Charité University, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Rodriguez-Laval
authors.affiliation: Department of Hepatology and Gastroenterology, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany.
authors.forename: Ulrich Frank
authors.initials: UF
authors.lastname: Pape
authors.affiliation: Clinical Division of Oncology, Medical University Graz, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Lipp
authors.affiliation: Department of Gastroenterology, Philipps-University of Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gress
authors.affiliation: Department of Hepatology and Gastroenterology, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.affiliation: Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy gianfranco.dellefave@uniroma1.it.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
mesh_terms: D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*
keywords: Disease progression; Ki67; Metastases; Neuroendocrine tumors; Prognosis; Risk score