Stereotactic Radiosurgery for Cushing's Disease: Results of an International, Multicenter Study

Context Cushing's disease (CD) due to ACTH-secreting pituitary tumors can be a management challenge. The outcomes of stereotactic radiosurgery (SRS) for CD are not fully defined.

Objective To better understand the outcomes of SRS for CD and its role in management.

Design International, multicenter, retrospective cohort analysis.

Setting Ten medical centers participating in the International Gamma Knife Research Foundation (IGKRF).

Patients Patients with CD with more than 6 months endocrine follow-up.

Intervention SRS using Gamma Knife radiosurgery.

Main Outcome Measures The primary outcome was endocrine remission. Radiologic response and adverse radiation effects were recorded.

Results A total of 278 patients (222 women, mean age: 41.4 years) met inclusion criteria for the study. Mean follow-up was 5.6 years (0.5–20.5 years). Twenty-two patients received SRS as a primary treatment for CD. Mean margin dose was 23.7 Gy. Cumulative initial biochemical remission was 80% at 10 years. Mean time to remission was 14.5 months. Recurrences occurred in 18% with an initial remission. Overall, the rate of durable endocrine remission was 64% at 10 years, and it was 68% among patients who received SRS as a primary treatment. Adverse radiation effects included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (p = 0.01), while both visual (p < 0.0001) and nonvisual cranial neuropathy (p = 0.02) were related to prior pituitary irradiation.

Conclusion SRS for CD is well tolerated and frequently results in initial remission. However, endocrine 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.