The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study

Yi-Chieh HungDepartment of Neurological Surgery, University of Virginia, Charlottesville, Virginia;
Departments of Neurosurgery and Surgery, Chi-Mei Medical Center, Tainan;
Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan;

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Cheng-Chia LeeDepartment of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei;
School of Medicine, National Yang-Ming University, Taipei, Taiwan;

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Huai-che YangDepartment of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei;

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Nasser MohammedDepartment of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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Kathryn N. KearnsDepartment of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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Ahmed M. NabeelGamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
Department of Neurosurgery, Benha University, Qalubya, Egypt;

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Khaled Abdel KarimGamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
Clinical Oncology, Ain Shams University, Cairo; and

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Reem M. Emad EldinGamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt

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Amr M. N. El-ShehabyGamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
Departments of Neurosurgery and

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Wael A. RedaGamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
Departments of Neurosurgery and

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Sameh R. TawadrosGamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
Departments of Neurosurgery and

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Roman LiscakDepartment of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague;

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Jana JezkovaDepartment of Endocrinology and Metabolism, 3rd Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic;

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L. Dade LunsfordDepartment of Neurological Surgery, University of Pittsburgh, Pennsylvania;

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Hideyuki KanoDepartment of Neurological Surgery, University of Pittsburgh, Pennsylvania;

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Nathaniel D. SistersonDepartment of Neurological Surgery, University of Pittsburgh, Pennsylvania;

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Roberto Martínez ÁlvarezRadiosurgery Unit, Hospital Ruber Internacional, Madrid, Spain;

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Nuria E. Martínez MorenoRadiosurgery Unit, Hospital Ruber Internacional, Madrid, Spain;

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Douglas KondziolkaDepartment of Neurosurgery, NYU Langone Health System, New York, New York;

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John G. GolfinosDepartment of Neurosurgery, NYU Langone Health System, New York, New York;

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Inga GrillsDepartment of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan;

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Andrew ThompsonDepartment of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan;

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Hamid Borghei-RazaviDepartment of Neurosurgery, Cleveland Clinic, Cleveland, Ohio;

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Tanmoy Kumar MaitiDepartment of Neurosurgery, Cleveland Clinic, Cleveland, Ohio;

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Gene H. BarnettDepartment of Neurosurgery, Cleveland Clinic, Cleveland, Ohio;

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James McInerneyDepartment of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania;

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Brad E. ZachariaDepartment of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania;

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Zhiyuan XuDepartment of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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Jason P. SheehanDepartment of Neurological Surgery, University of Virginia, Charlottesville, Virginia;

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OBJECTIVE

The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas.

METHODS

This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients’ clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications.

RESULTS

The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087).

CONCLUSIONS

In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.

ABBREVIATIONS

ACTH = adrenocorticotropic hormone; EBRT = external beam radiotherapy; GH = growth hormone; IRRF = International Radiosurgery Research Foundation; PRL = prolactin; SRS = stereotactic radiosurgery; TSH = thyroxine-stimulating hormone.
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Illustration from Bernstock et al. (pp 655–663). Copyright Joshua D. Bernstock, NIH/NINDS. Published with permission.

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