Colorectal liver metastases (CLM) significantly impact colon cancer patients, influencing survival based on systemic chemotherapy response. Traditional methods like tumor grading scores (e.g., tumor regression grade - TRG) for prognosis suffer from subjectivity, time constraints, and expertise demands. Current machine learning approaches often focus on radiological data, yet the relevance of histological images for survival predictions, capturing intricate tumor microenvironment

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... is gaining recognition. To address these limitations, we propose an end-to-end approach for automated prognosis prediction using histology slides stained with H&E and 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 feature maps. We use an attention-based approach that weighs the importance of different slide regions in producing the final classification results. We exploit the extracted features for the metastatic nodules and surrounding tissue to train a prognosis model. In parallel, we train a vision Transformer (ViT) in a knowledge distillation framework to replicate and enhance the performance of the prognosis prediction. In our evaluation on a clinical dataset of 258 patients, our approach demonstrates superior performance with c-indexes of 0.804 (0.014) for OS and 0.733 (0.014) for TTR. Achieving 86.9% to 90.3% accuracy in predicting TRG dichotomization and 78.5% to 82.1% accuracy for the 3-class TRG classification task, our approach outperforms comparative methods. Our proposed pipeline can provide automated prognosis for pathologists and oncologists, and can greatly promote precision medicine progress in managing CLM patients.