Machine Learning-Based Prediction of Pediatric Ulcerative Colitis Treatment Response using Diagnostic Histopathology

Abstract

Background and Aims: We previously reported clinical features associated with outcomes in pediatric ulcerative colitis (UC). Here we developed a histopathology model to predict corticosteroid-free remission (CSFR) on mesalamine therapy alone. Methods: Pre-treatment rectal biopsy slides were digitized in training and validation groups of 292 and 113 pediatric UC patients, respectively. Whole slide images (WSI) underwent pre-processing. Thirteen machine learning (ML) models were trained using 250 histomic features including texture, color, histogram, and nuclei. Feature importance was determined by the Gini index with the classifier re-trained using the top features. Results: 187571 informative patches from 292 training group patients (Male:53%; Age:13y (IQR:11-15); CSFR:41%) were trained on 13 ML classifiers. The best model was random forest (RF). Eighteen optimal histomic features were identified and trained, and the corresponding WSI AUROC was 0.89 (95%CI:0.71, 0.96), accuracy of 90% for CSFR. Features were re-trained on an independent real-world dataset of 113 patients and the model WSI AUROC was 0.85 (95%CI:0.75, 0.95), accuracy of 85%. Conclusion: Routine histopathology obtained at diagnosis contains histomic features associated with both UC treatment responses and underlying mechanisms of disease.