BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

3rd Department of Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Endocrinology and Metabolism University of Virginia Health System Charlottesville Virginia USA

Department of Endocrinology Centre de Recherche du CHUS Université de Sherbrooke Sherbrooke Quebec Canada

Department of Neurological Surgery University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

Department of Neurological Surgery University of Virginia Health System Charlottesville Virginia USA

Department of Neurosurgery Allegheny Health Network Pittsburgh Pennsylvania USA

Department of Neurosurgery Centre de Recherche du CHUS Université de Sherbrooke Sherbrooke Quebec Canada

Department of Neurosurgery Koç University School of Medicine Istanbul Turkey

Department of Neurosurgery NYU Langone Medical Center New York New York USA

Department of Neurosurgery Penn State Health Hershey Medical Center Hershey Pennsylvania USA

Department of Neurosurgery The University of Texas Health Science Center Houston Texas USA

Department of Radiation Oncology Mayo Clinic Jacksonville Jacksonville Florida USA

Department of Radiation Oncology NYU Langone Medical Center New York New York USA

Department of Radiation Oncology University of Virginia Health System Charlottesville Virginia USA

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

Division of Radiation Oncology Allegheny Health Network Cancer Institute Pittsburgh Pennsylvania USA

Division of Radiation Oncology University of Alberta Edmonton Alberta Canada

Radiology Department Dominican Gamma Knife Center CEDIMAT Santo Domingo Dominican Republic

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