Predicting Microsatellite Instability and Key Biomarkers in Colorectal Cancer from H&E-stained Images: Achieving State-of-the-art Predictive Performance with Fewer Data Using Swin Transformer

Many artificial intelligence models have been developed to predict clinically relevant biomarkers for colorectal cancer (CRC), including microsatellite instability (MSI). However, existing deep learning networks require large training datasets, which are often hard to obtain. In this study, based on the latest Hierarchical Vision Transformer using Shifted Windows (Swin Transformer [Swin-T]), we developed an efficient workflow to predict biomarkers in CRC (MSI, hypermutation, chromosomal instability, CpG island methylator phenotype, and BRAF and TP53 mutation) that required relatively small datasets. Our Swin-T workflow substantially achieved the state-of-the-art (SOTA) predictive performance in an intra-study cross-validation experiment on the Cancer Genome Atlas colon and rectal cancer dataset (TCGA-CRC-DX). It also demonstrated excellent generalizability in cross-study external validation and delivered a SOTA area under the receiver operating characteristic curve (AUROC) of 0.90 for MSI, using the Molecular and Cellular Oncology dataset for training (N = 1,065) and the TCGA-CRC-DX (N = 462) for testing. A similar performance (AUROC = 0.91) was reported in a recent study, using ~8,000 training samples (ResNet18) on the same testing dataset. Swin-T was extremely efficient when using small training datasets and exhibited robust predictive performance with 200-500 training samples. Our findings indicate that Swin-T could be 5-10 times more efficient than existing algorithms for MSI prediction based on ResNet18 and ShuffleNet. Furthermore, the Swin-T models demonstrated their capability in accurately predicting MSI and BRAF mutation status, which could exclude and therefore reduce samples before subsequent standard testing in a cascading diagnostic workflow, in turn reducing turnaround time and costs.