Multimodal Artificial Intelligence in Lung Cancer: From Data Integration to Precision Oncology.

Lung cancer remains the leading cause of cancer-related death globally, despite significant advances in diagnosis and treatment. Single biomarker approaches used clinically, such as programmed death ligand-1 (PD-L1) expression levels, have limited capacity for predicting treatment response. Multimodal data analysis using artificial intelligence (AI) offers an innovative scope to integrate diverse data sources-including radiologic imaging, digital pathology, genomics, immunohistochemistry, and Cell Painting morphology-to improve clinical predictions. This review aims to examine multimodal AI applications across the lung cancer treatment landscape related to such data sources. We analyze technical architectures spanning convolutional neural networks for imaging, vision transformers for pathology, and graph neural networks for genomics. We discuss how integrating and learning from heterogeneous data sources requires cross-attention fusion mechanisms. We further analyze critical studies demonstrating that multimodal AI clinical applications achieve superior predictive performance compared to unimodal biomarker methods. Multimodal AI models can augment clinicians in treatment selection, longitudinal monitoring using circulating tumor DNA (ctDNA), and variant interpretation through morphological profiling. We propose developing a multimodal AI model to optimize precision oncology for lung cancer.