CONTEXT: Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. OBJECTIVE: To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. DESIGN: International, multicenter, retrospective cohort analysis. SETTING: Ten medical centers participating in the International Gamma Knife Research Foundation. PATIENTS: Patients with CD with >6 months endocrine follow-up. INTERVENTION: SRS using Gamma Knife radiosurgery. MAIN OUTCOME MEASURES: The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. RESULTS: In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. CONCLUSIONS: SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS.

2nd Department of Medicine 3rd Faculty of Medicine of the Charles University Faculty Hospital Kralovske Vinohrady 11636 Prague Czech Republic

Clinical Oncology Department Gamma Knife Center Cairo Nasser Institute Ain Shams University Cairo Egypt 11566

Department of Functional Neurosurgery and Radiosurgery Ruber International Hospital 28034 Madrid Spain

Department of Medicine University of Virginia Health System Charlottesville Virginia 22908

Department of Neurologic Surgery University of Pittsburgh Medical Center Pittsburgh Pennsylvania 15213

Department of Neurologic Surgery University of Virginia Health System Charlottesville Virginia 22908

Department of Neurosurgery Neurologic Institute Taipei Veterans General Hospital Taipei 11217 Taiwan Republic of China

Department of Neurosurgery New York University Lagone Medical Center New York New York 10016

Department of Neurosurgery University of Pennsylvania Philadelphia Pennsylvania 19104

Department of Radiation Oncology Beaumont Health System Royal Oak Michigan 48073

Department of Stereotactic and Radiation Neurosurgery Na Homolce Hospital 11636 Prague Czech Republic

Division of Neurosurgery Université de Sherbrooke Centre de recherche du CHUS Sherbrooke Québec J1H 5N4 Canada

Neurosurgery Department Gamma Knife Center Cairo Nasser Institute Ain Shams University Cairo Egypt 11566

Neurosurgery Department Gamma Knife Center Cairo Nasser Institute Benha University Benha Egypt 11566

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