Semi-supervised ViT knowledge distillation network with style transfer normalization for colorectal liver metastases survival prediction

Colorectal liver metastases (CLM) affect almost half of all colon cancer patients and the response to systemic chemotherapy plays a crucial role in patient survival. While oncologists typically use tumor grading scores, such as tumor regression grade (TRG), to establish an accurate prognosis on patient outcomes, including overall survival (OS) and time-to-recurrence (TTR), these traditional methods have several limitations. They are subjective, time-consuming, and require extensive expertise, which limits their scalability and reliability. Additionally, existing approaches for prognosis prediction using machine learning mostly rely on radiological imaging data, but recently histological images have been shown to be relevant for survival predictions by allowing to fully capture the complex microenvironmental and cellular characteristics of the tumor. To address these limitations, we propose an end-to-end approach for automated prognosis prediction using histology slides stained with Hematoxylin and Eosin (H&E) and Hematoxylin Phloxine Saffron (HPS). We first employ a Generative Adversarial Network (GAN) for slide normalization to reduce staining variations and improve the overall quality of the images that are used as input to our prediction pipeline. We propose a semi-supervised model to perform tissue classification from sparse annotations, producing segmentation and feature maps. Specifically, we use an attention-based approach that weighs the importance of different slide regions in producing the final classification results. Finally, we exploit the extracted features for the metastatic nodules and surrounding tissue to train a prognosis model. In parallel, we train a vision Transformer model in a knowledge distillation framework to replicate and enhance the performance of the prognosis prediction. We evaluate our approach on an in-house clinical dataset of 258 CLM patients, achieving superior performance compared to other comparative models with a c-index of 0.804 (0.014) for OS and 0.735 (0.016) for TTR, as well as on two public datasets. The proposed approach achieves an accuracy of 86.9% to 90.3% in predicting TRG dichotomization. For the 3-class TRG classification task, the proposed approach yields an accuracy of 78.5% to 82.1%, outperforming the comparative methods. Our proposed pipeline can provide automated prognosis for pathologists and oncologists, and can greatly promote precision medicine progress in managing CLM patients.