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Received — 7 January 2026 ⏭ Favourites

MRD
PRIME: an interpretable artificial intelligence model based on liquid biopsy improves prediction of progression risk in non-small cell lung cancer Yu Wang · Yong-Bo Xiang · Xiao-Wei Chen · Tao Zhang · Jian-Yang Wang · Wen-Yang Liu · Lei Deng · Lu-Hua Wang · Shu-Geng Gao · Nan Bi
Mil Med Res. 2026 Jan 6;12(1):94. doi: 10.1186/s40779-025-00679-z.ABSTRACTBACKGROUND: Despite the predictive impact of circulating tumor DNA (ctDNA) minimal residual disease (MRD), accurate prediction of failure risk after curative-intent treatments for early-stage or localized non-small cell lung cancer (NSCLC) patients to guide personalized therapy remains challenging. This study aimed to develop and validate an interpretable artificial intelligence-assisted model using global data resources.M
6 January 2026 at 19:00

PRIME: an interpretable artificial intelligence model based on liquid biopsy improves prediction of progression risk in non-small cell lung cancer

MRD

By: Yu Wang · Yong-Bo Xiang · Xiao-Wei Chen · Tao Zhang · Jian-Yang Wang · Wen-Yang Liu · Lei Deng · Lu-Hua Wang · Shu-Geng Gao · Nan Bi

6 January 2026 at 19:00

Mil Med Res. 2026 Jan 6;12(1):94. doi: 10.1186/s40779-025-00679-z.

ABSTRACT

BACKGROUND: Despite the predictive impact of circulating tumor DNA (ctDNA) minimal residual disease (MRD), accurate prediction of failure risk after curative-intent treatments for early-stage or localized non-small cell lung cancer (NSCLC) patients to guide personalized therapy remains challenging. This study aimed to develop and validate an interpretable artificial intelligence-assisted model using global data resources.

METHODS: Liquid biopsy data, blood-based genomic alterations, clinicopathological features, and survival outcomes of stage I-III NSCLC patients who underwent surgery or definitive chemoradiotherapy were collected from 6 cohorts. PRIME (Progression Risk prediction by Interpretable Machine learning on ctDNA-MRD, Mutations, and clinical-therapeutic features) was trained by 6 machine learning algorithms across 4 cohorts and validated in 2 independent cohorts. Model performance was evaluated by the area under the curve (AUC) and interpreted by SHapley Additive exPlanations (SHAP). Whole-exome sequencing (WES) or whole-genome sequencing (WGS) of tumor tissue from 430 stage II-III NSCLC patients and RNA-sequencing (RNA-seq) data from 1149 subjects, sourced from The Cancer Genome Atlas, were used to validate the prognostic effect of mutations identified in peripheral blood and investigate the underlying mechanisms.

RESULTS: A global dataset encompassing 781 blood samples from 493 patients was analyzed. Clinical stage, pre-treatment ctDNA, post-treatment MRD, blood-based Kelch-like ECH-associated protein 1 (KEAP1), serine/threonine kinase 11 (STK11), and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations, and treatment modality were significantly associated with the risk of disease progression and were thereby included in the model training. WES/WGS and RNA-seq confirmed the poor prognostic effect of KEAP1, STK11, and CDKN2A mutations, which were characterized by the suppressive tumor microenvironment and attenuated humoral immunity. The neural network (NN) model exhibited optimal prediction of treatment failure risk in the training (AUC = 0.85, 95% CI 0.81-0.89) and validation sets (AUC = 0.82, 95% CI 0.74-0.89). SHAP analysis indicated that MRD (+0.306), treatment modality (+0.128), and pre-treatment ctDNA (+0.043) ranked in the top 3 contributions. NN-PRIME outperformed single liquid biopsy biomarkers and clinical-therapeutic signatures, and demonstrated consistent robustness across different clinical scenarios. High-risk patients identified by NN-PRIME had poorer prognoses but derived significant benefits from adjuvant therapy after surgery.

CONCLUSIONS: As an interpretable model integrating readily-accessible and crucial clinical-genomic predictors, PRIME achieves enhanced performance, allowing for early outcome prediction, refined risk stratification, and personalized clinical decision-making.

PMID:41491583 | PMC:PMC12771999 | DOI:10.1186/s40779-025-00679-z

cs.AI, q-bio.NC updates on arXiv.org
How to make Medical AI Systems safer? Simulating Vulnerabilities, and Threats in Multimodal Medical RAG System Kaiwen Zuo · Zelin Liu · Raman Dutt · Ziyang Wang · Zhongtian Sun · Fan Mo · Pietro Li\`o
arXiv:2508.17215v2 Announce Type: replace-cross Abstract: Large Vision-Language Models (LVLMs) augmented with Retrieval-Augmented Generation (RAG) are increasingly employed in medical AI to enhance factual grounding through external clinical image-text retrieval. However, this reliance creates a significant attack surface. We propose MedThreatRAG, a novel multimodal poisoning framework that systematically probes vulnerabilities in medical RAG systems by injecting adversarial image-text pairs. A
6 January 2026 at 13:00

How to make Medical AI Systems safer? Simulating Vulnerabilities, and Threats in Multimodal Medical RAG System

cs.AI, q-bio.NC updates on arXiv.org

By: Kaiwen Zuo · Zelin Liu · Raman Dutt · Ziyang Wang · Zhongtian Sun · Fan Mo · Pietro Li\`o

6 January 2026 at 13:00

arXiv:2508.17215v2 Announce Type: replace-cross Abstract: Large Vision-Language Models (LVLMs) augmented with Retrieval-Augmented Generation (RAG) are increasingly employed in medical AI to enhance factual grounding through external clinical image-text retrieval. However, this reliance creates a significant attack surface. We propose MedThreatRAG, a novel multimodal poisoning framework that systematically probes vulnerabilities in medical RAG systems by injecting adversarial image-text pairs. A key innovation of our approach is the construction of a simulated semi-open attack environment, mimicking real-world medical systems that permit periodic knowledge base updates via user or pipeline contributions. Within this setting, we introduce and emphasize Cross-Modal Conflict Injection (CMCI), which embeds subtle semantic contradictions between medical images and their paired reports. These mismatches degrade retrieval and generation by disrupting cross-modal alignment while remaining sufficiently plausible to evade conventional filters. While basic textual and visual attacks are included for completeness, CMCI demonstrates the most severe degradation. Evaluations on IU-Xray and MIMIC-CXR QA tasks show that MedThreatRAG reduces answer F1 scores by up to 27.66% and lowers LLaVA-Med-1.5 F1 rates to as low as 51.36%. Our findings expose fundamental security gaps in clinical RAG systems and highlight the urgent need for threat-aware design and robust multimodal consistency checks. Finally, we conclude with a concise set of guidelines to inform the safe development of future multimodal medical RAG systems.