Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome

Oncologist. 2017 Apr;22(4):409-415. doi: 10.1634/theoncologist.2016-0351. Epub 2017 Feb 23.

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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 Oncologist 2017;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.

Keywords: Disease progression; Ki67; Metastases; Neuroendocrine tumors; Prognosis; Risk score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression*
  • Disease-Free Survival
  • Female
  • Humans
  • Intestinal Neoplasms / diagnosis
  • Intestinal Neoplasms / epidemiology*
  • Intestinal Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / epidemiology*
  • Neuroendocrine Tumors / pathology*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatic Neoplasms / pathology*
  • Proportional Hazards Models
  • Risk Factors
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / pathology*

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor