title: Natural course and survival of neuroendocrine tumors of thymus and lung in MEN1 patients.
abstract: BACKGROUND
  The natural course and survival of neuroendocrine tumors (NETs) of thymus (Th) and lung in multiple endocrine neoplasia type 1 (MEN1) patients are still unknown.
  
  
  OBJECTIVE
  Our objective was to assess prevalence, tumor growth, and survival of Th and lung NETs in an unselected MEN1 population with long-term follow-up.
  
  
  METHODS
  This was an observational study.
  
  
  METHODS
  A longitudinal study was performed using the Dutch national MEN1 database, including >90% of the Dutch MEN1 population >16 years of age. Patients under care of the Dutch University Medical Centers (1990-2011) (n = 323) were included.
  
  
  METHODS
  The prevalence and survival of Th and lung NETs were assessed. Linear mixed-models analysis was applied to assess tumor growth with age as a possible confounder and gender, genotype and baseline tumor size as possible effect modifiers.
  
  
  RESULTS
  Th NETs occurred in 3.4% of patients, almost exclusively in males with a 10-year survival of 25% (95% confidence interval = 8%-80%). A thoracic computed tomography scan was available in 188 patients (58.2%). A lung NET was identified in 42 patients (13.0%) with a 10-year survival of 71.1% (95% confidence interval = 51%-100%). Tumor volume of lung NETs increased 17% per year (P < .001) (tumor doubling time 4.5 years). Tumor doubling time in males was 2.5 vs 5.5 years in females (P = .05). Lung NET growth was not associated with genotype or with baseline tumor size (<1 vs ≥1 cm).
  
  
  CONCLUSIONS
  In MEN1 patients, Th NETs almost exclusively occurred in males and had a very low prevalence and a high mortality. Lung NETs occurred more often than previously thought, had an indolent course, and occurred equally in both sexes. Tumor growth in males was double compared with female patients.
authors.affiliation: Departments of Internal Medicine (J.M.d.L., C.R.P., M.F.v.d.B., G.D.V.) and Surgery (M.R.V.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; Department of Clinical Epidemiology and Biostatistics (J.W.T.), VU University Medical Center, 1007 MB, Amsterdam, The Netherlands; Department of Endocrinology (A.R.H.), Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; Departments of Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University Medical Center, 6202 AZ Amsterdam, The Netherlands; Department of Endocrinology and Metabolism (P.H.B.), Academic Medical Center, 1100 DD Amsterdam, The Netherlands; and Department of Internal Medicine (B.H.), Division of Endocrinology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: de Laat
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Pieterman
authors.forename: Medard F
authors.initials: MF
authors.lastname: van den Broek
authors.forename: Jos W
authors.initials: JW
authors.lastname: Twisk
authors.forename: Ad R
authors.initials: AR
authors.lastname: Hermus
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Anouk N
authors.initials: AN
authors.lastname: van der Horst-Schrivers
authors.forename: Madeleine L
authors.initials: ML
authors.lastname: Drent
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bisschop
authors.forename: Bas
authors.initials: B
authors.lastname: Havekes
authors.forename: Menno R
authors.initials: MR
authors.lastname: Vriens
authors.forename: Gerlof D
authors.initials: GD
authors.lastname: Valk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000401:mortality*; D018358:Neuroendocrine Tumors / Q000401:mortality*; D015995:Prevalence; D011379:Prognosis; D013953:Thymus Neoplasms / Q000401:mortality*; D055815:Young Adult