BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. METHODS: Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. RESULTS: Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone ≥2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm 3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P -value = .004). CONCLUSION: For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.

Allegheny Health Network Cancer Institute and Allegheny Health Network Pittsburgh Pennsylvania USA

Department of Clinical Oncology Ain Shams University Cairo Egypt

Department of Neurological Surgery Hospices civils de Lyon Lyon France

Department of Neurological Surgery University of Virginia Charlottesville Virginia USA

Department of Neurosurgery Ain Shams University Cairo Egypt

Department of Neurosurgery Allegheny Health Network Pittsburgh Pennsylvania USA

Department of Neurosurgery Koc University School of Medicine Istanbul Turkey

Department of Neurosurgery NYU Langone New York New York USA

Department of Neurosurgery University of Miami Miami Florida USA

Department of Neurosurgery University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

Department of Radiation Oncology National Cancer Institute Cairo University Cairo Egypt

Department of Radiation Oncology NYU Langone New York New York USA

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

Department of Radiation Oncology University of Miami Miami Florida USA

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

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

Division of Neurosurgery Centre de recherche du CHUS Université de Sherbrooke Sherbrooke Quebec Canada

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

Drexel University College of Medicine Philadelphia Pennsylvania USA

Gamma Knife Center Cairo Nasser institute Hospital Cairo Egypt

Neurosurgery Department Faculty of Medicine Benha University Qalubya Egypt

Neurosurgery Department Military Medical Academy Cairo Egypt

University of Virginia School of Medicine Charlottesville Virginia USA

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