Lumi-Guide: An Artificial-Intelligence-Driven Multimodal Framework for Optimizing Personalized Neoadjuvant Therapy...

Accurate prediction of pathological complete response (pCR) to neoadjuvant therapy in luminal breast cancer remains challenging, hindering precise treatment decisions. Here, we present the Lumi-Guide system, a novel multimodal framework that integrates deep-learning-based MRI analysis with clinical and genomic data to enable personalized treatment selection. In this multicenter study, we analyzed 1,097 patients with luminal breast cancer from 6 international datasets. We developed a Swin Transformer-based Lumi-I model using 3-plane dynamic contrast-enhanced MRI data and integrated it with clinical factors to construct the Lumi-CI model, which demonstrated robust performance across the validation and 2 external test sets, with areas under the receiver operating characteristic curves of 0.810, 0.819, and 0.864, respectively. Radiogenomic analysis revealed distinct biological characteristics: The Lumi-I high-score group exhibited immunologically active and proliferative microenvironments, while the low-score group showed estrogen-response-driven signaling. To further enhance predictive accuracy, a genomic model (Lumi-G) based on 22 established RNA biomarkers was further developed and integrated with the Lumi-CI model to create a multimodal Lumi-CIG model. We subsequently designed a Lumi-Guide 2-step triage system that prioritizes clinical-imaging information (Lumi-CI) while selectively incorporating genomic data (Lumi-CIG) when beneficial, thus optimizing resource allocation. Critically, by integrating Lumi-Guide system prestratification with response-predictive-subtype-recommended therapies, patients predicted to achieve pCR demonstrated substantially higher actual pCR rates than controls across 3 treatment patterns: 77.8% vs. 61.5% (optimal treatment), 57.6% vs. 24.7% (non-optimal treatment), and 35.3% vs. 4.7% (double-negative response-predictive subtype). This clinically practical and biologically interpretable framework transforms personalized neoadjuvant therapy in luminal breast cancer into a scalable reality.