Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study

I. Jonathan Pomeraniec Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia;

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Hideyuki Kano Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and

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Zhiyuan Xu Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia;

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Brandon Nguyen Department of Radiation Oncology, William Beaumont Hospital–Royal Oak, Michigan;

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Zaid A. Siddiqui Department of Radiation Oncology, William Beaumont Hospital–Royal Oak, Michigan;

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Danilo Silva Cleveland Clinic Foundation, Center for Neurological Restoration, Cleveland, Ohio;

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Mayur Sharma Cleveland Clinic Foundation, Center for Neurological Restoration, Cleveland, Ohio;

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Hesham Radwan Cleveland Clinic Foundation, Center for Neurological Restoration, Cleveland, Ohio;

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Jonathan A. Cohen Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and

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Robert F. Dallapiazza Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia;

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Christian Iorio-Morin Department of Neurosurgery, Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada;

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Amparo Wolf Department of Neurosurgery, NYU Langone Medical Center, New York, New York;

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John A. Jane Jr. Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia;

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Inga S. Grills Department of Radiation Oncology, William Beaumont Hospital–Royal Oak, Michigan;

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David Mathieu Department of Neurosurgery, Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada;

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Douglas Kondziolka Department of Neurosurgery, NYU Langone Medical Center, New York, New York;

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Cheng-Chia Lee Department of Neurosurgery, Taipei Veterans General Hospital, Taipei City, Taiwan;

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Chih-Chun Wu Department of Neurosurgery, Taipei Veterans General Hospital, Taipei City, Taiwan;

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Christopher P. Cifarelli Department of Neurosurgery, West Virginia University Medical Center, Morgantown, West Virginia

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Tomas Chytka Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic;

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Gene H. Barnett Cleveland Clinic Foundation, Center for Neurological Restoration, Cleveland, Ohio;

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L. Dade Lunsford Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and

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Jason P. Sheehan Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia;

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OBJECTIVE

Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome.

METHODS

This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery.

RESULTS

After matching, 222 patients met the authors’ study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32).

CONCLUSIONS

In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

ABBREVIATIONS

ACTH = adrenocorticotrophic hormone; AP = anteroposterior; CC = craniocaudal; GKRS = Gamma Knife radiosurgery; NFPA = nonfunctioning pituitary adenoma; SRS = stereotactic radiosurgery; TR = transverse.
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