title: Effective time window in reducing pituitary adenoma size by gamma knife radiosurgery.
abstract: OBJECTIVE
  Although the effectiveness of gamma knife radiosurgery (GKRS) in controlling the size of pituitary adenomas has been well demonstrated in many studies, the time period in which significant changes in tumor size occurs has been investigated in a limited fashion. It is important to determine the therapeutic window of GKRS in treating pituitary adenomas, i.e., the effective timeframe during which significant size reduction of these tumors occurs, so that alternative treatments such as further GKRS or microsurgery might be prescribed in a timely manner if clinically indicated.
  
  
  METHODS
  This was a nested sample of an ongoing local cohort study on GKRS for pituitary adenomas at the University of Virginia. Magnetic resonance imaging (MRI) using dedicated sequences was employed. Only patients with a baseline MRI (TP0) and at least 1 follow-up study performed in the University Hospital after GKRS were included. The follow-up scans were performed at five time-points (TP1-TP5) which were 6, 12, 24, 36 and 48 months after GKRS. The dimensional indices of the tumors were measured in three orthogonal planes, i.e., transverse (TR), antero-posterior (AP) and cranio-caudal (CC). The volumes of the tumors were estimated by using the following formula: [Formula: see text]. Tumor volume decrease by more than 25% from baseline was considered as 'shrinkage', <25% tumor size increase or decrease was considered 'static', and more than 25% increase as 'increment'. Our cohort consisted of 21 patients, with functioning adenomas in 13 subjects i.e. six adrenocorticotrophic hormone (ACTH)-secreting and seven growth hormone (GH)-secreting, and non-functioning (NF) adenomas in eight subjects.
  
  
  RESULTS
  In 26 adenomas (8 ACTH, 9 GH and 9 NF), tumor control (tumor shrinkage or static) were achieved in 21 tumors (80.8%); 89, 75, and 78% for GH-secreting, ACTH-secreting and NF adenomas respectively, at the end of the 4-year follow-up period. Analysis of variance showed significant differences of GKRS margin dose among different types of tumors (p = 0.013), but not of baseline tumor volumes (p = 0.240). Logistic regression analysis showed no significant association of margin dose, baseline volume or tumor type with the tumor control outcome. Comparison of tumor change using dimensional indices relative to the base time point (TP0) showed that in the sample there was an average reduction of 1.290 mm at TP1 (6 months) with p values 0.155 (parametric t test) and 0.098 (non-parametric Wilcoxon signed-ranked test) respectively, showing a moderate reduction in tumor dimensional indices. The change in dimensional indices at later time points (TP2-TP5) showed an average reduction ranging from 1.930 to 2.471 mm. Significant reduction in the mean dimensional indices was firstly observed at TP2 (1 year) with p values 0.013 (t test) and 0.018 (Wilcoxon signed-rank test). Such scale of reduction in the dimensional indices appeared to be maintained along the time axis (from TP2 to TP5).
  
  
  CONCLUSIONS
  Significant decrease in tumor dimensional indices tended to occur at 1 year post-GKRS. Although to a lesser extent, such decrease in dimensional indices continued up to the end of our follow-up period.
authors.affiliation: Department of Diagnostic Radiology, University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Henry Ka-Fung
authors.initials: HK
authors.lastname: Mak
authors.forename: Shui-Wun
authors.initials: SW
authors.lastname: Lai
authors.forename: Wenshu
authors.initials: W
authors.lastname: Qian
authors.forename: Stanley
authors.initials: S
authors.lastname: Xu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tong
authors.forename: May Lee
authors.initials: ML
authors.lastname: Vance
authors.forename: Edward
authors.initials: E
authors.lastname: Oldfield
authors.forename: John
authors.initials: J
authors.lastname: Jane
authors.forename: Jason
authors.initials: J
authors.lastname: Sheehan
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: Yau
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000473:pathology / Q000601:surgery*; D000236:Adenoma / Q000473:pathology / Q000601:surgery*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000473:pathology / Q000601:surgery; D016634:Radiosurgery; D013997:Time Factors; D047368:Tumor Burden