CoRe-WM: Conditioned Response-State World Modeling for Longitudinal Treatment-Response Prediction in Breast DCE-MRI

Pathologic complete response (pCR) after neoadjuvant chemotherapy is a key prognostic indicator in aggressive breast cancer, yet existing prediction approaches either rely on pretreatment imaging alone, missing the patient's evolving response, or optimize multi-visit classifiers under direct outcome supervision, coupling representation learning with the clinical endpoint. We formulate longitudinal pCR prediction as a world-modeling problem and propose Conditioned Response-state World Modeling (CoRe-WM), which learns a latent state-transition model that predicts the next imaging state from the observed sequence. The transition function is conditioned on patient clinical profile and assigned therapy through additive shift and feature-wise modulation, enabling patient- and treatment-specific dynamics. A Factorized Response State pathway further decouples treatment-response dynamics from imaging appearance by encoding the structural prior that response manifests primarily in lesion morphology. After pretraining, all parameters are frozen and a linear readout predicts pCR at each clinical decision point. We evaluate CoRe-WM on I-SPY2 under five-fold cross-validation and assess cross-cohort transfer on I-SPY1. CoRe-WM achieves the highest discrimination among all evaluated methods at every prospective decision point, and demonstrates robust cross-cohort transfer. Ablation studies identify patient-profile conditioning and the factorized response pathway as the principal contributors. These results establish world-model-based representation learning as a promising framework for outcome prediction in oncology and beyond.