Patient-Level Effectiveness Prediction Modeling for Glioblastoma Using Classification Trees
Geldof, Tine Van Damme, Nancy Huys, Isabelle Van Dyck, Walter
Geldof, Tine
Van Damme, Nancy
Huys, Isabelle
Van Dyck, Walter
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Journal article with impact factor
Editor
Supervisor
Publication Year
2020
Journal
Frontiers in Pharmacology
Book
Publication Volume
10
Publication Issue
January
Publication Begin page
1
Publication End page
10
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Abstract
OBJECTIVES: Little research has been done in pharmacoepidemiology on the use of machine learning for exploring medicinal treatment effectiveness in oncology. Therefore, the aim of this study was to explore the added value of machine learning methods to investigate individual treatment responses for glioblastoma patients treated with temozolomide.
METHODS: Based on a retrospective observational registry covering 3090 patients with glioblastoma treated with temozolomide, we proposed the use of a two-step iterative exploratory learning process consisting of an initialization phase and a machine learning phase. For initialization, we defined a binary response variable as the target label using one-by-one nearest neighbor propensity score matching. Secondly, a classification tree algorithm was trained and validated for dividing individual patients into treatment response and non-response groups. Theorizing about treatment response was then done by evaluating the tree performance.
RESULTS: The classification tree model has an area under the curve (AUC) classification performance of 67% corresponding to a sensitivity of 0.69 and a specificity of 0.51. This result in predicting patient-level response was slightly better than the logistic regression model featuring an AUC of 64% (0.63 sensitivity and 0.54 specificity). The tree confirms confounding by age and discovers further age-related stratification with chemotherapy-treatment dependency, both not revealed in preceding clinical studies. The model lacked genetic information confounding treatment response.
CONCLUSIONS: A classification tree was found to be suitable for understanding patient-level effectiveness for this glioblastoma-temozolomide case because of its high interpretability and capability to deal with covariate interdependencies, essential in a real-world environment. Possible improvements in the model's classification can be achieved by including genetic information and collecting primary data on treatment response. The model can be valuable in clinical practice for predicting personal treatment pathways.
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Keywords
32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, Machine Learning and Artificial Intelligence, Genetics, Brain Cancer, Precision Medicine, Cancer, Brain Disorders, Networking and Information Technology R&D (NITRD), Rare Diseases, 6.1 Pharmaceuticals