TrajOnco: a multi-agent framework for temporal reasoning over longitudinal EHR for multi-cancer early detection

Modeling patient trajectories from longitudinal electronic health records (EHRs) requires reasoning over sparse, noisy, and long-context multimodal sequences. Existing LLM-based multi-agent systems address context length but process patients in isolation, failing to mirror how clinicians leverage accumulated experience from similar prior cases. We present Traj-Evolve, a self-evolving multi-agent system with two complementary evolving mechanisms. First, an Experience Pool (ExPool) acts as a non-parametric memory, indexing rejection-sampled reasoning traces to retrieve similar patients as few-shot contexts. Second, multi-agent reinforcement learning (MARL) via reward-ranked fine-tuning parametrically optimizes inter-agent and agent-memory collaboration. A leave-one-out cross-retrieval strategy unifies the two, aligning training- and inference-time behavior under retrieval augmentation. On a lung cancer prediction task utilizing up to five years of multimodal EHRs, Traj-Evolve outperforms 9 strong baselines on the overall population and a challenging never-smoker population. Analysis of the evolving dynamics highlights three key findings: (1) expanding the ExPool shifts optimal retrieval from diverse to specific samples; (2) under MARL, the manager agent's prediction loss converges quickly while the worker agents' temporal reasoning continues to benefit from more verified patients; and (3) the two mechanisms are complementary on the predicted risk, where ExPool improves specificity while MARL improves sensitivity.

As large language models empower healthcare, intelligent clinical decision support has developed rapidly. Longitudinal electronic health records (EHR) provide essential temporal evidence for accurate clinical diagnosis and analysis. However, current large language models have critical flaws in longitudinal EHR reasoning. First, lacking fine-grained statistical reasoning, they often hallucinate clinical trends and metrics when quantitative evidence is textually implied, biasing diagnostic inference. Second, non-uniform time series and scarce labels in longitudinal EHR hinder models from capturing long-range temporal dependencies, limiting reliable clinical reasoning. To address the above limitations, this work presents the Probabilistic Chain-of-Thought Completion Agent (COTCAgent), a hierarchical reasoning framework for longitudinal electronic health records. It consists of three core modules. The Temporal-Statistics Adapter (TSA) converts analytical plans into executable code for standardized trend output. The Chain-of-Thought Completion (COTC) layer leverages a symptom-trend-disease knowledge base with weighted scoring to evaluate disease risk, while the bounded completion module acquires structured evidence through standardized inquiries and iterative scoring constraints to ensure rigorous reasoning. By decoupling statistical computation, feature matching, and language generation, the framework eliminates reliance on complex multi-modal inputs and enables efficient longitudinal record analysis with lower computational overhead. Experimental results show that COTCAgent powered by Baichuan-M2 achieves 90.47% Top-1 accuracy on the self-built dataset and 70.41% on HealthBench, outperforming existing medical agents and mainstream large language models. The code is available at https://github.com/FrankDengAI/COTCAgent/.

Longitudinal electronic health records (EHRs) contain complementary diagnostic and laboratory information about patient health. However, irregularity, sparsity, heterogeneity, and incompleteness in documentation complicate EHR modeling. To address the problem, we introduce GraphBEAT (Graph-based Bucketized Event Aggregation over Time), a temporal graph representation learning framework that groups clinical events into time buckets and transforms observed features into patient-specific, temporally directed graphs to enable early risk stratification for gastrointestinal cancers. Each node in an EHR graph encodes feature identity, observed value, and temporal position of clinical events. A context-aware, time-decay message-passing mechanism models transitions between successive buckets, followed by multi-head attention pooling to generate patient-level representations. GraphBEAT was trained and evaluated on multi-site longitudinal diagnosis codes and laboratory tests to predict pancreatic, liver, and intestinal cancer at 12-, 24-, and 36-month diagnostic lead times. In all experimental setups, GraphBEAT consistently outperformed baseline graph neural networks (GraphSAGE, GAT, and GCN) and sequence modeling approaches (Transformer and long short-term memory [LSTM]). GraphBEAT also required over 250x fewer floating-point operations per patient and over 20x fewer parameters than the Transformer and LSTM baselines. These results support GraphBEAT as an accurate and computationally efficient approach for cancer risk stratification from sparse, heterogeneous longitudinal health records.