Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: a matched-cohort analysis

Georgios MantziarisDepartment of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;

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Stylianos PikisDepartment of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;

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

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

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Kimball SheehanDepartment of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;

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Darrah SheehanDepartment of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;

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Selcuk PekerDepartment of Neurosurgery, Koc University School of Medicine, Istanbul, Turkey;

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Yavuz SamanciDepartment of Neurosurgery, Koc University School of Medicine, Istanbul, Turkey;

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Shray K. BindalDepartment of Neurological Surgery, University of Pittsburgh, Pennsylvania;

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Ajay NiranjanDepartment of Neurological Surgery, University of Pittsburgh, Pennsylvania;

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

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Rupinder KaurDepartment of Neurosurgery and Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India;

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Renu MadanDepartment of Neurosurgery and Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India;

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Manjul TripathiDepartment of Neurosurgery and Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India;

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Dhiraj J. PangalDepartment of Neurosurgery, Keck School of Medicine of USC, Los Angeles, California;

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Ben A. StricklandDepartment of Neurosurgery, Keck School of Medicine of USC, Los Angeles, California;

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Gabriel ZadaDepartment of Neurosurgery, Keck School of Medicine of USC, Los Angeles, California;

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Anne-Marie LangloisDivision of Neurosurgery, Université de Sherbrooke, Centre de recherché du CHUS, Sherbrooke, Québec, Canada;

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David MathieuDivision of Neurosurgery, Université de Sherbrooke, Centre de recherché du CHUS, Sherbrooke, Québec, Canada;

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Ronald E. WarnickGamma Knife Center, Jewish Hospital, Mayfield Clinic, Cincinnati, Ohio;

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Samir PatelDivision of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; and

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Zayda MinierDepartment of Radiology, Dominican Gamma Knife Center and CEDIMAT, Santo Domingo, Dominican Republic

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Herwin SpeckterDepartment of Radiology, Dominican Gamma Knife Center and CEDIMAT, Santo Domingo, Dominican Republic

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

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Rithika Kormath AnandDepartment of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;

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

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OBJECTIVE

Radiological progression occurs in 50%–60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs.

METHODS

This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed.

RESULTS

Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55–4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6–12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = −0.8%, p > 0.99) or visual deficits (RD = −2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01).

CONCLUSIONS

SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

ABBREVIATIONS

ADJ = adjuvant; GTR = gross-total resection; IQR = interquartile range; NFPA = nonfunctioning pituitary adenoma; PRG = progression; RD = risk difference; SRS = stereotactic radiosurgery; STR = subtotal resection.
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