title: Cerebrovascular events, secondary intracranial tumors, and mortality after radiotherapy for nonfunctioning pituitary adenomas: a subanalysis from the Dutch National Registry of Growth Hormone Treatment in Adults.
abstract: BACKGROUND
  Radiotherapy is frequently administered as adjuvant treatment in patients with clinically nonfunctioning pituitary adenomas (NFPAs). However, concerns have been raised about potential long-term side effects, including cerebrovascular events (CVEs) and secondary intracranial tumors.
  
  
  OBJECTIVE
  The aim of this study was to analyze the risk of CVEs, secondary intracranial tumors, and mortality in irradiated (IRR) NFPA patients, compared with NFPA patients who were not irradiated (non-IRR).
  
  
  METHODS
  The study cohort included 806 patients with a NFPA from the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide long-term surveillance study in severe GH-deficient adult patients. IRR patients (n = 456) were compared with non-IRR patients (n = 350).
  
  
  METHODS
  CVEs, secondary intracranial tumors, and mortality were measured.
  
  
  RESULTS
  Sixty-nine subjects developed a CVE. In men, but not in women, the incidence of a CVE was significantly higher in IRR patients than in non-IRR patients (hazard ratio 2.99, 95% confidence interval 1.31-6.79). A secondary intracranial tumor developed in five IRR patients and two non-IRR patients. After adjustment for age, radiotherapy was not associated with mortality.
  
  
  CONCLUSIONS
  The incidence of secondary intracranial tumors and mortality did not differ between IRR and non-IRR patients. However, a CVE was found significantly more frequently in IRR men but not in women. Further research into the long-term effects of cranial radiotherapy seems mandatory. The potential risks of radiotherapy have to be taken into account when radiotherapy is considered in NFPA patients, and long-term follow-up is recommended.
authors.affiliation: Department of Internal Medicine (N.C.v.V., C.C.v.B., D.H.H.U., M.L.D.), Endocrine Section, Neuroscience Campus Amsterdam, VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Department of Internal Medicine (A.A.M.F.), Isala Clinics, 8000 GK Zwolle, The Netherlands; Emotional Brain and Alan Turing Institute for Multidisciplinary Health Research (H.P.F.K.), 1311 RL Almere, The Netherlands; and Division of Endocrinology and Metabolism (A.J.v.d.L.), Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: N C
authors.initials: NC
authors.lastname: van Varsseveld
authors.forename: C C
authors.initials: CC
authors.lastname: van Bunderen
authors.forename: D H H
authors.initials: DH
authors.lastname: Ubachs
authors.forename: A A M
authors.initials: AA
authors.lastname: Franken
authors.forename: H P F
authors.initials: HP
authors.lastname: Koppeschaar
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: M L
authors.initials: ML
authors.lastname: Drent
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000556:secondary; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000453:epidemiology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000401:mortality*; D016609:Neoplasms, Second Primary / Q000401:mortality*; D009426:Netherlands / Q000453:epidemiology; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D012042:Registries; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D016019:Survival Analysis
chemical_list: D019382:Human Growth Hormone