K. Bressem
Publications
Agentic clinical reasoning over longitudinal myeloma records: a retrospective evaluation against expert consensus
Multiple myeloma is managed through sequential lines of therapy over years to decades, with each decision depending on cumulative disease history distributed across dozens to hundreds of heterogeneous clinical documents. Whether LLM-based systems can synthesise this evidence at a level approaching expert agreement has not been established. A retrospective evaluation was conducted on longitudinal clinical records of 811 myeloma patients treated at a tertiary centre (2001-2026), covering 44,962 documents and 1,334,677 laboratory values, with external validation on MIMIC-IV. An agentic reasoning system was compared against single-pass retrieval-augmented generation (RAG), iterative RAG, and full-context input on 469 patient-question pairs from 48 templates at three complexity levels. Reference labels came from double annotation by four oncologists with senior haematologist adjudication. Iterative RAG and full-context input converged on a shared ceiling (75.4% vs 75.8%, p = 1.00). The agentic system reached 79.6% concordance (95% CI 76.4-82.8), exceeding both baselines (+3.8 and +4.2 pp; p = 0.006 and 0.007). Gains rose with question complexity, reaching +9.4 pp on criteria-based synthesis (p = 0.032), and with record length, reaching +13.5 pp in the top decile (n = 10). The system error rate (12.2%) was comparable to expert disagreement (13.6%), but severity was inverted: 57.8% of system errors were clinically significant versus 18.8% of expert disagreements. Agentic reasoning was the only approach to exceed the shared ceiling, with gains concentrated on the most complex questions and longest records. The greater clinical consequence of residual system errors indicates that prospective evaluation in routine care is required before these findings translate into patient benefit.
Agentic retrieval-augmented reasoning reshapes collective reliability under model variability in radiology question answering
Agentic retrieval-augmented reasoning pipelines are increasingly used to structure how large language models (LLMs) incorporate external evidence in clinical decision support. These systems iteratively retrieve curated domain knowledge and synthesize it into structured reports before answer selection. Although such pipelines can improve performance, their impact on reliability under model variability remains unclear. In real-world deployment, heterogeneous models may align, diverge, or synchronize errors in ways not captured by accuracy. We evaluated 34 LLMs on 169 expert-curated publicly available radiology questions, comparing zero-shot inference with a radiology-specific multi-step agentic retrieval condition in which all models received identical structured evidence reports derived from curated radiology knowledge. Agentic inference reduced inter-model decision dispersion (median entropy 0.48 vs. 0.13) and increased robustness of correctness across models (mean 0.74 vs. 0.81). Majority consensus also increased overall (P<0.001). Consensus strength and robust correctness remained correlated under both strategies (\r{ho}=0.88 for zero-shot; \r{ho}=0.87 for agentic), although high agreement did not guarantee correctness. Response verbosity showed no meaningful association with correctness. Among 572 incorrect outputs, 72% were associated with moderate or high clinically assessed severity, although inter-rater agreement was low (\k{appa}=0.02). Agentic retrieval therefore was associated with more concentrated decision distributions, stronger consensus, and higher cross-model robustness of correctness. These findings suggest that evaluating agentic systems through accuracy or agreement alone may not always be sufficient, and that complementary analyses of stability, cross-model robustness, and potential clinical impact are needed to characterize reliability under model variability.