Machine learning-based clinical outcome prediction in surgery for acromegaly

Purpose: Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. Methods: Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. Results: The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. Conclusions: Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.