Prognostic factors and survival in MEN1 patients with gastrinomas: Results from the DutchMEN study group (DMSG)

J Surg Oncol. 2019 Nov;120(6):966-975. doi: 10.1002/jso.25667. Epub 2019 Aug 10.

Abstract

Background and objectives: Gastrinomas are the most prevalent functioning neuroendocrine tumors (NET) in multiple endocrine neoplasia type 1 (MEN1). Guidelines suggest medical therapy in most patients, but surgery may be considered in a subgroup. Currently, factors to guide management are necessary. This population-based cohort study assessed prognostic factors of survival in patients with MEN1-related gastrinomas.

Methods: Patients with MEN1 having gastrinomas were identified in the Dutch MEN1 database from 1990 to 2014 based on fasting serum gastrin (FSG) levels and/or pathology. Predictors of overall survival were assessed using Cox regression.

Results: Sixty-three patients with gastrinoma (16% of the MEN1 population) were identified. Five- and 10-year overall survival rates were 83% and 65%, respectively. Prognostic factors associated with overall survival were initial FSG levels ≥20x upper limit of normal (ULN) (hazard ratio [HR], 6.2 [95% confidence interval, 1.7-23.0]), pancreatic NET ≥2 cm (HR 4.5; [1.5-13.1]), synchronous liver metastases (HR 8.9; [2.1-36.7]), gastroduodenoscopy suspicious for gastric NETs (HR 12.7; [1.4-115.6]), and multiple concurrent NETs (HR 5.9; [1.2-27.7]).

Conclusion: Life expectancy of patients with MEN1 gastrinoma is reduced. FSG levels and pancreatic NETs ≥2 cm are prognostic factors. FSG levels might guide surveillance intensity, step-up to additional diagnostics, or provide arguments in selecting patients who might benefit from surgery.

Keywords: Zollinger-Ellison syndrome; multiple endocrine neoplasia type 1; neuroendocrine tumor; oncology.

MeSH terms

  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gastrinoma / metabolism
  • Gastrinoma / mortality*
  • Gastrinoma / pathology
  • Gastrinoma / surgery
  • Humans
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / mortality*
  • Intestinal Neoplasms / pathology
  • Intestinal Neoplasms / surgery
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Netherlands
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / mortality*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / surgery
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Proto-Oncogene Proteins / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Rate

Substances

  • MEN1 protein, human
  • Proto-Oncogene Proteins

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor