Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas

Ahmed Shaaban Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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Chloé Dumot Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia;
Department of Neurological Surgery, Hospices Civils de Lyon, France;

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Georgios Mantziaris Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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Sam Dayawansa Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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Selcuk Peker Department of Neurosurgery, Koç University School of Medicine, Istanbul, Turkey;

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Yavuz Samanci Department of Neurosurgery, Koç University School of Medicine, Istanbul, Turkey;

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Ahmed M. Nabeel Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt;
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Wael A. Reda Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt;
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Sameh R. Tawadros Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt;
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Khaled Abdel Karim Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt;
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Amr M. N. El-Shehaby Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt;
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Reem M. Emad Eldin Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt;
Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt;

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Ahmed Ragab Abdelsalam Neurosurgery Department, Military Medical Academy, Cairo, Egypt; and

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Roman Liscak Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic;

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Jaromir May Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic;

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Elad Mashiach Departments of Neurosurgery and

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Fernando De Nigris Vasconcellos Departments of Neurosurgery and

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Kenneth Bernstein Radiation Oncology, NYU Langone, New York, New York;

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Douglas Kondziolka Departments of Neurosurgery and

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Herwin Speckter Dominican Gamma Knife Center and Radiology Department, CEDIMAT, Santo Domingo, Dominican Republic;

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Ruben Mota Dominican Gamma Knife Center and Radiology Department, CEDIMAT, Santo Domingo, Dominican Republic;

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Anderson Brito Dominican Gamma Knife Center and Radiology Department, CEDIMAT, Santo Domingo, Dominican Republic;

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Shray K. Bindal University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;

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Ajay Niranjan University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;

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L. Dade Lunsford University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;

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Carolina Gesteira Benjamin Departments of Neurosurgery and

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Timoteo Almeida Radiation Oncology, University of Miami, Florida;

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Jennifer Z. Mao Departments of Neurosurgery and

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David Mathieu Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Québec, Canada;

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Jean-Nicolas Tourigny Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Québec, Canada;

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Manjul Tripathi Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India;

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Joshua David Palmer Department of Radiation Oncology, The James Cancer Hospital at The Ohio State University, Columbus, Ohio;

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Jennifer Matsui Department of Radiation Oncology, The James Cancer Hospital at The Ohio State University, Columbus, Ohio;

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Joseph Crooks Drexel University College of Medicine, Philadelphia, Pennsylvania; and

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Rodney E. Wegner Allegheny Health Network Cancer and Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania

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Matthew J. Shepard Allegheny Health Network Cancer and Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania

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Jason P. Sheehan Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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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.

ABBREVIATIONS

ACTH = adrenocorticotropic hormone; IGF-1 = insulin-like growth factor–1; NFPA = nonfunctioning pituitary adenoma; SRS = stereotactic radiosurgery; TSH = thyroid-stimulating hormone.
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