Advanced gastrointestinal stromal tumor: reliable classification of imatinib plasma trough concentration via machine learning

Abstract

Aim: Patients with advanced gastrointestinal stromal tumors (GISTs) exhibiting an imatinib plasma trough concentration (IM C_min) under 1100 ng/ml may show a reduced drug response rate, leading to the suggestion of monitoring for IM C_min. Consequently, the objective of this research was to create a customized IM C_min classification model for patients with advanced GISTs from China.

Methods: Initial data and laboratory indicators from patients with advanced GISTs were gathered, and the above information was segmented into a training set, validation set, and testing set in a 6:2:2 ratio. Key variables associated with IM C_min were identified to construct the classification model using the least absolute shrinkage and selection operator (LASSO) regression and forward stepwise binary logistic regression. Within the training and validation sets, nine ML classification models were constructed via the resampling method and underwent comparison through the Brier scores, the areas under the receiver-operating characteristic curve (AUROC), the decision curve, and the precision-recall (AUPR) curve to determine the most suitable model for this dataset. Two methods of internal validation were used to assess the most suitable model's classification performance: tenfold cross-validation and random split-sample validation (test set), and the value of the test set AUROC was used to evaluate the model's classification performance.

Results: Six key variables (gender, daily IM dose, metastatic site, red blood cell count, platelet count, and percentage of neutrophils) were ultimately selected to construct the classification model. In the validation set, it is found by comparison that the Extreme Gradient Boosting (XGBoost) model has the largest AUROC, the lowest Brier score, the largest area under the decision curve, and the largest AUPR value. Furthermore, as evaluated via internal verification, it also performed well in the test set (AUROC = 0.725).

Conclusion: For patients with advanced GISTs who receive IM, initial data and laboratory indicators could be used to accurately estimate whether the IM C_min is below 1100 ng/ml. The XGBoost model may stand a chance to assist clinicians in directing the administration of IM.

Keywords: Gastrointestinal stromal tumor; Imatinib; Machine learning; Plasma trough concentration; Therapeutic drug monitoring.