title: Gamma Knife surgery for patients with nonfunctioning pituitary macroadenomas: predictors of tumor control, neurological deficits, and hypopituitarism.
abstract: OBJECTIVE
  Nonfunctioning pituitary macroadenomas often recur after microsurgery and thereby require further treatment. Gamma Knife surgery (GKS) has been used to treat recurrent adenomas. In this study, the authors evaluated outcomes following GKS of nonfunctioning pituitary macroadenomas and assessed predictors of tumor control, neurological deficits, and delayed hypopituitarism.
  
  
  METHODS
  Between June 1989 and March 2010, 140 consecutive patients with nonfunctioning pituitary macroadenomas were treated using GKS at the University of Virginia. The median patient age was 51 years (range 21-82 years), and 56% of patients were male. Mean tumor volume was 5.6 cm3 (range 0.6-35 cm3). Thirteen patients were treated with GKS as primary therapy, and 127 had undergone at least 1 open resection prior to GKS. Ninety-three patients had a history of hormone therapy prior to GKS. The mean maximal dose of GKS was 38.6 Gy (range 10-70 Gy), the mean marginal dose was 18 Gy (range 5-25 Gy), and the mean number of isocenters was 9.8 (range 1-26). Follow-up evaluations were performed in all 140 patients, ranging from 0.5 to 17 years (mean 5 years, median 4.2 years).
  
  
  RESULTS
  Tumor volume remained stable or decreased in 113 (90%) of 125 patients with available follow-up imaging. Kaplan-Meier analysis demonstrated radiographic progression free survival at 2, 5, 8, and 10 years to be 98%, 97%, 91%, and 87%, respectively. In multivariate analysis, a tumor volume greater than 5 cm3 (hazard ratio=5.0, 95% CI 1.5-17.2; p=0.023) was the only factor predictive of tumor growth. The median time to tumor progression was 14.5 years. Delayed hypopituitarism occurred in 30.3% of patients. No factor was predictive of post-GKS hypopituitarism. A new or worsening cranial nerve deficit occurred in 16 (13.7%) of 117 patients. Visual decline was the most common neurological deficit (12.8%), and all patients experiencing visual decline had evidence of tumor progression. In multivariate analysis, a tumor volume greater than 5 cm3 (OR=3.7, 95% CI 1.2-11.7; p=0.025) and pre-GKS hypopituitarism (OR=7.5, 95% CI 1.1-60.8; p=0.05) were predictive of a new or worsened neurological deficit.
  
  
  CONCLUSIONS
  In patients with nonfunctioning pituitary macroadenomas, GKS confers a high rate of tumor control and a low rate of neurological deficits. The most common complication following GKS is delayed hypopituitarism, and this occurs in a minority of patients.
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Starke
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Williams
authors.forename: John A
authors.initials: JA
authors.lastname: Jane
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000236:Adenoma / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003389:Cranial Nerve Diseases / Q000209:etiology / Q000503:physiopathology; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology*; D010907:Pituitary Hormones / Q000097:blood; D010911:Pituitary Neoplasms / Q000601:surgery*; D011183:Postoperative Complications / Q000209:etiology*; D011237:Predictive Value of Tests; D011379:Prognosis; D011874:Radiometry; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010907:Pituitary Hormones