Stereotactic radiosurgery (SRS) is frequently used for Cushing's disease (CD) after failed pituitary surgery. Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks. The outcomes of repeat pituitary radiosurgery, however, have not been described. We sought to determine the outcomes of repeat SRS in patients with CD. We pooled data from five institutions participating in the International Gamma Knife Research Foundation for patients with recurrent or persistent CD ≥ 12 months after initial SRS. Patients were included in the study if they had ≥ 6 months endocrine follow-up after repeat SRS. Twenty patients were included in the study. Repeat single-session SRS was performed 1.3-9.7 years after initial SRS. Median endocrine follow-up was 6.6 years (1.4-19.1 years). Median margin dose was 20 Gy (range 10.8-35 Gy). Endocrine remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range 2-64 months). Biochemical recurrence occurred in two patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual loss and permanent diplopia. Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected patients with hypercortisolism confirmed one or more years after initial SRS.

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

Department of Functional Neurosurgery and Radiosurgery Ruber International Hospital Madrid Spain

Department of Medicine University of Virginia Health System Charlottesville VA USA

Department of Neurological Surgery University of Pittsburgh Medical Center Pittsburgh PA USA

Department of Neurosurgery Barrow Neurological Institute Phoenix AZ USA

Department of Neurosurgery M D Anderson Cancer Center Houston TX USA

Department of Neurosurgery Neurological Institute Taipei Veterans General Hospital Taipei Taiwan Republic of China

Department of Neurosurgery University of Virginia Medical Center P O Box 800212 Charlottesville VA 22908 USA

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

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