TRAPS: Therapeutic Response Analysis via Pathway-informed Stratification

Cancer treatment planning requires decisions across multiple clinical dimensions at once. Clinicians must determine whether a patient should receive targeted molecular therapy, radiation therapy, and whether they are likely to survive beyond six months. Existing pathway-informed deep learning models have been developed and tested in isolation, making fair comparison across architectures impossible. We present the first unified benchmark for pathway-guided therapy response modeling, evaluating three biologically informed architectures, BINN, GraphPath, and PATH, across five cancer cohorts drawn from The Cancer Genome Atlas, representing 2,622 patients encoded using Reactome pathway activity scores. Each model is trained jointly on all three clinical outcomes under identical data and evaluation conditions, the first study to treat pathway-structured deep learning as a combined therapy and survival prediction problem. Our results show that no single architecture wins across all tasks: PATH performs best for targeted molecular therapy prediction overall, BINN is most reliable for survival prediction, and no model produces useful predictions for radiation therapy, as the key drivers of that decision are clinical variables not captured in gene expression data. Most strikingly, GraphPath achieves an AUROC of 0.92 on prostate targeted molecular therapy prediction, the highest score in the entire benchmark, demonstrating that lateral co-regulation structure produces exceptional discriminative power when matched to a cohort with a narrow targetable driver programme, even under conditions of extreme class imbalance at only 11\% positive prevalence.

Improving the Safety and Trustworthiness of Medical AI via Multi-Agent Evaluation Loops

Large Language Models (LLMs) are increasingly applied in healthcare, yet ensuring their ethical integrity and safety compliance remains a major barrier to clinical deployment. This work introduces a multi-agent refinement framework designed to enhance the safety and reliability of medical LLMs through structured, iterative alignment. Our system combines two generative models - DeepSeek R1 and Med-PaLM - with two evaluation agents, LLaMA 3.1 and Phi-4, which assess responses using the American Medical Association's (AMA) Principles of Medical Ethics and a five-tier Safety Risk Assessment (SRA-5) protocol. We evaluate performance across 900 clinically diverse queries spanning nine ethical domains, measuring convergence efficiency, ethical violation reduction, and domain-specific risk behavior. Results demonstrate that DeepSeek R1 achieves faster convergence (mean 2.34 vs. 2.67 iterations), while Med-PaLM shows superior handling of privacy-sensitive scenarios. The iterative multi-agent loop achieved an 89% reduction in ethical violations and a 92% risk downgrade rate, underscoring the effectiveness of our approach. This study presents a scalable, regulator-aligned, and cost-efficient paradigm for governing medical AI safety.