Upfront Gamma Knife radiosurgery for Cushing’s disease and acromegaly: a multicenter, international study

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Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing’s disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas.


An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor median margin dose of 25 Gy (range 12–40.0 Gy) at a median isodose of 50%.


The median endocrine follow-up was 69.5 months (range 9–246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2.


Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to patients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly.

ABBREVIATIONS ACTH = adrenocorticotropic hormone; CD = Cushing’s disease; CN = cranial nerve; CS = cavernous sinus; GH = growth hormone; GKS = Gamma Knife radiosurgery; IGF-I = insulin-like growth factor–I; SRS = stereotactic radiosurgery; UFC = urinary free cortisol.

Article Information

Correspondence Jason P. Sheehan: University of Virginia Health System, Charlottesville, VA. jsheehan@virginia.edu.

INCLUDE WHEN CITING Published online August 17, 2018; DOI: 10.3171/2018.3.JNS18110.

Disclosures Dr. Lunsford reports stock ownership in Elekta AB. He is also on the Data and Safety Monitoring Board for Insightec.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Kaplan-Meier plot showing that actuarial endocrine remission rates after GKS for the entire study cohort at 1, 2, 3, and 5 years were 23%, 35%, 42%, and 51%, respectively. The number with follow-up at 1, 2, 3, and 5 years was 33, 27, 22, and 14 patients, respectively.

  • View in gallery

    Kaplan-Meier plot demonstrating differential endocrine remission rates after upfront GKS in patients with adenoma secreting GH and CD. Patients with CD were more likely to achieve remission (p = 0.0005) than those with acromegaly. The number with follow-up at 1, 2, 3, and 5 years was 10, 6, 4, and 2 patients, respectively, for CD and 25, 21, 17, and 12 patients, respectively, for acromegaly.



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