Development of a Machine Learning-Based Prediction Model for Chemotherapy-Induced Myelosuppression in Children with Wilms’ Tumor

SIMPLE SUMMARY: Wilms’ tumor is the most common renal malignant tumor in children, and chemotherapy is an indispensable part of the treatment for most Wilms’ tumor patients. Chemotherapy-induced myelosuppression is the most common and serious toxicity of chemotherapy, which can hinder the process of chemotherapy and even endanger life. However, there is a lack of tools to predict chemotherapy-induced myelosuppression. We herein develop a model based on machine learning that can effectively predict the risk of chemotherapy-induced myelosuppression in children with Wilms’ tumor, offering the possibility to identify children with high risk of chemotherapy-induced myelosuppression early and take preventive strategies. ABSTRACT: Purpose: Develop and validate an accessible prediction model using machine learning (ML) to predict the risk of chemotherapy-induced myelosuppression (CIM) in children with Wilms’ tumor (WT) before chemotherapy is administered, enabling early preventive management. Methods: A total of 1433 chemotherapy cycles in 437 children with WT who received chemotherapy in our hospital from January 2009 to March 2022 were retrospectively analyzed. Demographic data, clinicopathological characteristics, hematology and blood biochemistry baseline results, and medication information were collected. Six ML algorithms were used to construct prediction models, and the predictive efficacy of these models was evaluated to select the best model to predict the risk of grade ≥ 2 CIM in children with WT. A series of methods, such as the area under the receiver operating characteristic curve (AUROC), the calibration curve, and the decision curve analysis (DCA) were used to test the model’s accuracy, discrimination, and clinical practicability. Results: Grade ≥ 2 CIM occurred in 58.5% (839/1433) of chemotherapy cycles. Based on the results of the training and validation cohorts, we finally identified that the extreme gradient boosting (XGB) model has the best predictive efficiency and stability, with an AUROC of up to 0.981 in the training set and up to 0.896 in the test set. In addition, the calibration curve and the DCA showed that the XGB model had the best discrimination and clinical practicability. The variables were ranked according to the feature importance, and the five variables contributing the most to the model were hemoglobin (Hgb), white blood cell count (WBC), alkaline phosphatase, coadministration of highly toxic chemotherapy drugs, and albumin. Conclusions: The incidence of grade ≥ 2 CIM was not low in children with WT, which needs attention. The XGB model was developed to predict the risk of grade ≥ 2 CIM in children with WT for the first time. The model has good predictive performance and stability and has the potential to be translated into clinical applications. Based on this modeling and application approach, the extension of CIM prediction models to other pediatric malignancies could be expected.