OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Allegheny Health Network Cancer and Department of Neurosurgery Allegheny Health Network Pittsburgh Pennsylvania

Clinical Oncology Ain Shams University Cairo Egypt

Department of Neurological Surgery Hospices Civils de Lyon France

Department of Neurological Surgery University of Virginia Charlottesville Virginia

Department of Neurosurgery Koç University School of Medicine Istanbul Turkey

Department of Neurosurgery Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Radiation Oncology National Cancer Institute Cairo University Cairo Egypt

Department of Radiation Oncology The James Cancer Hospital at The Ohio State University Columbus Ohio

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

Departments of11Neurosurgery and

Departments of15Neurosurgery and

Departments of6Neurosurgery and

Division of Neurosurgery Université de Sherbrooke Centre de Recherche du CHUS Sherbrooke Québec Canada

Dominican Gamma Knife Center and Radiology Department CEDIMAT Santo Domingo Dominican Republic

Drexel University College of Medicine Philadelphia Pennsylvania; and

Gamma Knife Center Cairo Nasser Institute Hospital Cairo Egypt

Neurosurgery Department Faculty of Medecine Benha University Qalubya Egypt

Neurosurgery Department Military Medical Academy Cairo Egypt; and

Radiation Oncology NYU Langone New York New York

Radiation Oncology University of Miami Florida

University of Pittsburgh School of Medicine Pittsburgh Pennsylvania

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