A Multimodal Foundation Model for Longitudinal Patient Representation and Scalable Insight Generation in Oncology

Precision oncology necessitates a longitudinal model of patient state that captures cancer evolution and treatment over time, integrating multimodal observations. We introduce the oFM, a foundation model developed on a real-world oncology cohort of 1.67 million cancer patients that integrates clinical trajectories with DNA, RNA, and H&E pathology. Patient-level partitions were reserved for training, validation, and testing, with over one million patients used for training. The oFM encodes daily clinical and molecular episodes and, along with pathology images, integrates them over time to produce a patient state embedding. We evaluate frozen oFM embeddings against expert-curated clinical and molecular baseline features. In prognostic benchmarks, the oFM improved AUC for treatment response, progression-free survival, and overall survival (0.774 vs. 0.563 for overall survival). Across 11 comparative-treatment cohorts, the oFM embeddings achieved a three-fold higher pooled and scale-normalized treatment-benefit AUTOC than baseline features with improved benefit ranking in 9 of 11 cohorts, and provided stronger prognostic discrimination within both treatment arms. We also evaluated a mechanism discovery framework that interprets downstream models built on oFM embeddings by linking their predicted outcomes to clinically and biologically grounded mechanisms through an evidence-grounded temporal graph, enabling evaluation in clinical and drug-development applications.

PatTree: a novel approach for automated creation of multimodal, graph-based patient representations for medical classification tasks

Access to holistic, multimodal data improves the performance of Artificial Intelligence (AI) in medical classification tasks compared to utilizing single modalities or data sources. However, the inherent heterogeneity and complexity of clinical real-world data pose significant challenges to structured data analysis and AI application. This heterogeneity includes missing values, multiple time points, diverse modalities, and inconsistent formats and semantics. Data harmonization prior to data integration tackles this challenge but remains resource-intensive and error-prone, limiting the scalability and reproducibility of holistic, AI-driven decision support on clinical real-world data. We therefore propose PatTree, a graph-based, holistic representation of patients that can be derived from real-world clinical data through the automated structuring of multimodal clinical data. PatTree enables early-stage data integration without relying on pre-standardized inputs. While representing heterogeneous clinical data within a unified knowledge graph, PatTree preserves the semantic relationships between data elements across modalities and data sources, facilitating interoperability and machine-interpretable data access. Using a subset of the ADNI-1 cohort (n = 763), we demonstrate that classification of patients is directly feasible on PatTree reaching state-of-the-art classification performance. In the three-class classification task distinguishing Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals, we achieve a balanced accuracy of 98.5% and an F$_1$ score of 0.987 on the held-out test set. Our results show that assumption-free, automated structuring of multimodal medical data can serve as a scalable foundation for clinical AI pipelines bypassing tedious data preparation and standardization.