Objective. To develop an artificial intelligence method predicting lymph node metastasis (LNM) for patients with colorectal cancer (CRC). Impact Statement. A novel interpretable multimodal AI-based method to predict LNM for CRC patients by integrating information of pathological images and serum tumor-specific biomarkers. Introduction. Preoperative diagnosis of LNM is essential in treatment planning for CRC patients. Existing radiology imaging and genomic tests approaches are either unreliable or too costly. Methods. A total of 1338 patients were recruited, where 1128 patients from one centre were included as the discovery cohort and 210 patients from other two centres were involved as the external validation cohort. We developed a Multimodal Multiple Instance Learning (MMIL) model to learn latent features from pathological images and then jointly integrated the clinical biomarker features for predicting LNM status. The heatmaps of the obtained MMIL model were generated for model interpretation. Results. The MMIL model outperformed preoperative radiology-imaging diagnosis and yielded high area under the curve (AUCs) of 0.926, 0.878, 0.809, and 0.857 for patients with stage T1, T2, T3, and T4 CRC, on the discovery cohort. On the external cohort, it obtained AUCs of 0.855, 0.832, 0.691, and 0.792, respectively (T1-T4), which indicates its prediction accuracy and potential adaptability among multiple centres. Conclusion. The MMIL model showed the potential in the early diagnosis of LNM by referring to pathological images and tumor-specific biomarkers, which is easily accessed in different institutes. We revealed the histomorphologic features determining the LNM prediction indicating the model ability to learn informative latent features.
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