Longitudinal 3D Foundation Modeling for Neoadjuvant Breast Cancer Response Prediction from Serial DCE-MRI

Pathologic complete response (pCR) is an important endpoint in neoadjuvant chemotherapy (NAC) for breast cancer, and predicting pCR from imaging during treatment could support treatment response assessment. Many existing imaging-based approaches rely on a single static timepoint, which fails to capture changes that occur during treatment. In this work, we present a longitudinal framework that combines a frozen 3D foundation encoder (Pillar-0) with our Temporal Dynamics Network (TDN) to predict treatment response from serial Dynamic Contrast-Enhanced (DCE) MRI acquired across four clinical timepoints from pre-treatment to pre-surgery. The TDN combines time-aware volumetric embeddings with clinical and treatment data to predict pCR. Evaluated on 982 patients from the combined I-SPY2 and ACRIN-6698 cohort, the proposed model achieves strong performance across all reported metrics when longitudinal 3D imaging is fused with clinical data (test AUROC: 73.6%, balanced accuracy: 69.1%). While clinical variables provide the strongest individual predictive signal, longitudinal 3D imaging contributes complementary information when fused with clinical data, improving pCR prediction. Our source code is available at: https://github.com/omarftt/longitudinal_temporal_pillar.

Beyond Random Partitioning: Unsupervised Spatio-Temporal Stratification for Cohort Balancing in Longitudinal Medical Imaging

Rigorous dataset partitioning is a foundational, yet frequently overlooked, prerequisite for reliable deep learning in longitudinal medical imaging. Naively shuffling small clinical cohorts routinely introduces covariate shifts and temporal sampling imbalances across training, validation, and test subsets, exposing downstream models to out-of-distribution evaluation. We address this vulnerability with an auditable Tripartite Dataset Analytics Framework that systematically characterizes spatial grid integrity, multi-parametric intensity fingerprints, and longitudinal temporal trajectories, quantifying the heavy-tailed feature dispersion and irregular, episodic sampling intervals typical of real-world clinical cohorts. Building on this characterization, we formalize an unsupervised spatio-temporal cohort-balancing standard operating procedure (SOP) that combines elbow-optimized K-means clustering over a standardized, six-dimensional joint intensity-temporal feature space with intra-cluster proportionate stratified sampling. On a longitudinal, contrast-enhanced $T1$-weighted brain MRI cohort (N=149), the protocol reduces the maximum cross-subset intensity bias from 34.1% under conventional random shuffling to under 2.1%, while aligning longitudinal follow-up intervals closely around the population mean. Monte Carlo stress testing across ten random seeds and three split configurations confirms that this alignment remains tightly bounded, in clear contrast to the substantial variability of random partitioning. The resulting protocol offers a reproducible, generalizable procedure for cohort engineering in variable-length longitudinal clinical imaging workflows.