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Predictive modeling for pituitary adenomas: single center experience in 501 consecutive patients

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Abstract

Background

Personalized postoperative management of patients with pituitary adenomas requires an early risk stratification system.

Methods

We reviewed 501 cases operated between 10/27/2011 and 5/5/2016 by a single neurosurgeon. We determined biochemical remission and tumor resection at 3 months, and biochemical recurrence, tumor recurrence, radiation and reoperation during follow-up. We considered age, gender, tumor diameter, cavernous sinus invasion (CSI) by MRI, diagnostic category (clinical, biochemical and immunohistochemical), and proliferation markers in a Cox proportional hazards model. We built predictive models with the significant parameters and used Kaplan–Meier survival curves for time-dependent analyses.

Results

The 501 cases comprised 141 functional and 360 nonfunctional adenomas. Tumor diameter, CSI, and ki-67 index predicted long-term events. Model 1 (CSI, diameter ≥ 2.9 cm and ki-67 > 3%) identified 18 (3.6%) adenomas and predicted persistent hypersecretory syndrome and residual tumor with 98.7% specificity (OR 8.6; CI 3.0–24.7). Model 2 (ki-67 > 3% and CSI) identified 48 (9.6%) adenomas and had 93.1% specificity (OR 3.3; CI 1.8–6.0). Model 3 (ki-67 > 3%, mitoses and p53, former “atypical” adenoma) identified 26 (5.2%) adenomas and had 96.0% specificity (OR 2.3; CI 1.0–5.0). Model 1 best predicted the long-term event-free survival and was strengthened when Knosp 3–4 CSI grades were used. Model 2 better identified the smaller adenomas at risk. Among the WHO 2017 special PA subtypes, patients with silent corticotroph adenoma had a lower event-free survival than ACTH-negative nonfunctional adenomas.

Conclusion

Use of CSI, ki-67 and tumor diameter in prediction models facilitates tailored surveillance and management of patients with pituitary adenomas.

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Abbreviations

CSI:

Cavernous sinus invasion

PPV:

Positive predictive value

NPV:

Negative predictive value

SD:

Standard deviation

CD:

Cushing’s disease

ACM:

Acromegaly

NFA:

Non-functional adenoma

SCA:

Silent ACTH-positive adenoma

ACTH:

Adrenocorticotropic hormone

PA:

Pituitary adenomas

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Acknowledgements

Emilee Wehunt, research coordinator responsible for regulatory aspects pertaining to this study.

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Correspondence to A. G. Ioachimescu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of Emory’s institutional and/or national research committee.

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Pappy, A.L., Savinkina, A., Bicknese, C. et al. Predictive modeling for pituitary adenomas: single center experience in 501 consecutive patients. Pituitary 22, 520–531 (2019). https://doi.org/10.1007/s11102-019-00982-8

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