Sheehan 2013 (Cushing's Disease SRS)

Background

Multicenter prospective cohort (International Radiosurgery Research Foundation, 11 North American centers). N=96 Cushing's disease after failed primary transsphenoidal surgery, treated with Gamma Knife SRS; marginal dose chosen to keep optic apparatus <8 Gy.

Interventions and follow up

Treatment: Gamma Knife SRS for Cushing's disease after failed transsphenoidal surgery; marginal dose set to keep optic apparatus <8 Gy
Primary endpoint: Endocrine remission (UFC normalization ± loss of diurnal variation); time to remission; new pituitary hormone deficiency
mFollow up: Median 49 mo

Results

Endocrine remission (UFC normalization): 54.2% (52/96)
Median time to remission: 16.5 mo
5-yr remission (Kaplan-Meier): 70%
New hypopituitarism: 36.4%

Adverse events

New hypopituitarism (any axis): 36.4% (GH and ACTH most common)
New visual deficit: 2.1%
New cranial nerve palsy: 1.0%
Deaths / radiation-induced neoplasia: None in cohort

Conclusions

SRS achieves ~70% 5-yr endocrine remission in Cushing's disease with persistent/recurrent disease after transsphenoidal surgery, median time to remission 16.5 mo. New hypopituitarism in ~36% is acceptable given the morbidity of untreated hypercortisolism. Among the largest prospective multicenter series for SRS in Cushing's.

Key Limitations

Non-randomized cohort; pooled multicenter biochemical criteria; no comparator (medical/repeat surgery); delayed remission with risk of interim hypercortisolism; relapse possible after initial remission.

Clinical Context

Supports SRS as second-line for Cushing's disease after failed transsphenoidal surgery; medical therapy bridges hypercortisolism during the latency to radiosurgical remission.

References