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

• Published in: Pituitary 2019-10, Vol.22 (5), p.520-531
• Main Authors: Pappy, A. L., Savinkina, A., Bicknese, C., Neill, S., Oyesiku, N. M., Ioachimescu, A. G.
• Format: Article
• Language: English
• Subjects: Adenoma; Adenoma - mortality; Adenoma - surgery; Adrenocorticotropic hormone; Adult; Disease-Free Survival; Endocrinology; Female; Human Physiology; Humans; Kaplan-Meier Estimate; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medicine; Medicine & Public Health; Middle Aged; Mitosis; Neoplasm Recurrence, Local; p53 Protein; Pituitary; Pituitary Neoplasms - mortality; Pituitary Neoplasms - surgery; Prediction models; Proportional Hazards Models; Remission; Survival; Tumors
• ISSN: 1386-341X; 1573-7403
• DOI: 10.1007/s11102-019-00982-8

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.