Lymph node metastasis prediction from in-situ lung squamous cell carcinoma histopathology images using deep learning.

Lung squamous cell carcinoma (LUSC), a subtype of non-small cell lung cancer, represents a significant portion of lung cancer cases with distinct histologic patterns impacting prognosis and treatment. The current pathological assessment methods face limitations such as inter-observer variability, necessitating more reliable techniques. This study seeks to predict lymph node metastasis in LUSC using deep learning models applied to histopathology images of primary tumors, offering a more accurate and objective method for diagnosis and prognosis. Whole slide images (WSIs) from the Outdo-LUSC and TCGA-LUSC cohorts were used to train and validate deep-learning models. Multi-instance learning was applied, with patch-level predictions aggregated into WSI-level outcomes. The study employed the ResNet-18 network, transfer learning, and rigorous data preprocessing. To represent WSI features, innovative techniques like patch likelihood histogram (PLH) and bag of words (BoW) were used, followed by training of machine learning classifiers, including the ExtraTrees algorithm. The diagnostic model for lymph node metastasis showed strong performance, particularly using the ExtraTrees algorithm, as demonstrated by receiver operating characteristic (ROC) curves and Grad-CAM visualizations. The signature generated by the ExtraTrees algorithm, named LN_ISLUSCH (lymph node status-related in-situ lung squamous cell carcinoma histopathology), achieved an area under the curve (AUC) of 0.941 (95% CI: 0.926-0.955) in the training set and 0.788 (95% CI: 0.748-0.827) in the test set. Kaplan-Meier analyses confirmed that the LN_ISLUSCH model was a significant prognostic factor (p = 0.02). This study underscores the potential of artificial intelligence in enhancing diagnostic precision in pathology. The LN_ISLUSCH model stands out as a promising tool for predicting lymph node metastasis and prognosis in LUSC. Future studies should focus on larger and more diverse cohorts and explore the integration of additional omics data to further refine predictive accuracy and clinical utility.