Cognitive functioning in untreated glioma patients: The limited predictive value of clinical variables

Abstract

Background: Previous research identified many clinical variables that are significantly related to cognitive functioning before surgery. It is not clear whether such variables enable accurate prediction for individual patients’ cognitive functioning because statistical significance does not guarantee predictive value. Previous studies did not test how well cognitive functioning can be predicted for (yet) untested patients. Furthermore, previous research is limited in that only linear or rank-based methods with small numbers of variables were used. Methods: We used various machine learning models to predict preoperative cognitive functioning for 340 patients with glioma across 18 outcome measures. Predictions were made using a comprehensive set of clinical variables as identified from the literature. Model performances and optimized hyperparameters were interpreted. Moreover, Shapley additive explanations were calculated to determine variable importance and explore interaction effects. Results: Best-performing models generally demonstrated above-random performance. Performance, however, was unreliable for 14 out of 18 outcome measures with predictions worse than baseline models for a substantial number of train-test splits. Best-performing models were relatively simple and used most variables for prediction while not relying strongly on any variable. Conclusions: Preoperative cognitive functioning could not be reliably predicted across cognitive tests using the comprehensive set of clinical variables included in the current study. Our results show that a holistic view of an individual patient likely is necessary to explain differences in cognitive functioning. Moreover, they emphasize the need to collect larger cross-center and multimodal data sets.