CoRe-WM: Conditioned Response-State World Modeling for Longitudinal Treatment-Response Prediction in Breast DCE-MRI
Authors: Lin Zhao, Bowen Chen, Qiaohui Gao, Shaowen Wan, Xiang Li, Wei Liu, Tianming Liu
Organizations: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA. · College of Engineering, Northeastern University, Boston, MA 02115, USA. · Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA. · Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ 85054, USA. · School of Computing, University of Georgia, Athens, GA 30602, USA.
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.
Figures & tables
Fig. 1 : Overview of CoRe-WM . (A) Outcome-free pretraining. The upper pathway encodes DCE-MRI visits into latent states and predicts the next latent via a conditioned causal Transformer; the lower pathway operates on lesion geometry descriptors to produce a factorized response state s^t+1 , which corrects the latent prediction and is supervised by the IRG loss. Patient profile, treatment, and temporal embeddings condition both pathways through FiLM modulation [ 43 ] . The EMA target encoder [ 44 ] provides the stable prediction target. (B) pCR prediction. All parameters are frozen; accumulated response states at each decision point are passed to a linear readout for progressively updated pCR estimates.
Method
Avail. MRI
AUROC
AUPRC
Acc.
Sens.
Spec.
Pretreatment methods
ViT [ 23 ]
T0
0.5591±0.0320
0.4064±0.0156
0.5657±0.0507
0.5164±0.1935
0.5917±0.1741
ViT + two-stage fusion [ 23 ]
T0
0.5950±0.0130
0.4230±0.0194
0.5521±0.0629
0.5745±0.2431
0.5412±0.2194
3-D ResNet
T0
0.5444±0.0391
0.3685±0.0242
0.4977±0.0617
0.6836±0.1546
0.4022±0.1661
Longitudinal methods
PrefixGRU
T0–T2
0.5784±0.0668
0.4157±0.0799
0.5718±0.0514
0.4982±0.2075
0.6098±0.1709
Temp. repr. learning [ 34 ]
T0–T2
0.5179±0.0516
0.3710±0.0559
0.5606±0.0476
0.3527±0.2079
0.6678±0.1748
Two-stage dual-task [ 33 ]
T0–T1
0.6958±0.0193
0.5412±0.0378
0.6435±0.0323
0.5745±0.0539
0.6792±0.0600
TABLE I : Five-fold I-SPY2 comparison using the same patient splits and seed for all methods. Values are fold mean ± standard deviation. The “Available MRI” column lists the examinations used by the pCR predictor; T3 may additionally be used as an outcome-free pretraining target ( CoRe-WM and BSTNet temporal-order pretraining). ViT two-stage fusion uses the complete BreastDCEDL clinical and geometry feature set. Accuracy, sensitivity, and specificity use a validation-selected threshold.
Method
Avail. MRI
AUROC (95% CI)
AUPRC
Acc.
Sens.
Spec.
Pretreatment methods
ViT [ 23 ]
T0
0.5584[0.4549,0.6609]
0.3159
0.4872
0.6829
0.4174
ViT + two-stage fusion [ 23 ]
T0
0.5750[0.4764,0.6746]
0.3276
0.4487
0.6585
0.3739
3-D ResNet
T0
0.6738[0.5698,0.7709]
0.4213
0.2949
0.9512
0.0609
Longitudinal methods
PrefixGRU
T0–T2
0.6494[0.5510,0.7428]
0.3798
0.6282
0.6341
0.6261
Temp. repr. learning [ 34 ]
T0–T2
0.5548[0.4519,0.6579]
0.3433
0.7308
0.0732
0.9652
Two-stage dual-task [ 33 ]
T0–T1
0.7635[0.6780,0.8402]
0.5391
0.7372
0.2439
0.9130
TABLE II : Cross-cohort transfer from I-SPY2 to 156 I-SPY1 patients (41 pCR). AUROC brackets are patient-bootstrap 95% confidence intervals. All pCR supervision, model selection, and operating-threshold selection use I-SPY2 only.
Cumulative configuration
Profile
Tx
Geo
FRS/IRG
AUROC
Δ AUROC
Image-only JEPA
–
–
–
–
0.5816±0.0316
–
+ patient profile
✓
–
–
–
0.7135±0.0117
+0.1319±0.0350
+ treatment conditioning
✓
✓
–
–
0.7115±0.0393
−0.0019±0.0467
+ ROI geometry
✓
✓
✓
–
0.7380±0.0138
+0.0264±0.0451
+ factorized response state
✓
✓
✓
FRS
0.7506±0.0473
+0.0126±0.0442
+ image-derived response guidance ( CoRe-WM )
✓
✓
✓
FRS+IRG
0.7545±0.0468
+0.0039±0.0082
TABLE III : Cumulative five-fold ablation at T0–T1. Values are fold mean ± standard deviation. Δ AUROC is relative to the preceding row. Patient profile includes HR, HER2, MammaPrint, and age; Tx denotes treatment conditioning; Geo denotes ROI geometry. FRS and IRG denote factorized response state and image-derived response guidance, respectively.
Fig. 2 : Five-fold diagnostic analyses. (a) OOF calibration curves at three prospective decision points; points show equal-frequency bins with Wilson 95% CIs. (b) Decision-curve analysis for non-pCR identification; shaded regions are bootstrap 95% CIs. (c) Condition-dependence analysis; MRI latents and geometry are fixed while treatment, clinical profile, or their joint context is permuted; shaded regions show ±1 SD across folds. (d) Response-state grounding; a ridge probe maps the frozen T0-to-T2 state update to observed log-volume shrinkage in 791 OOF patients.
Subtype
n (pCR%)
T0
T0–T1
T0–T2 (95% CI)
Overall
808
(34.0)
0.733
0.755
0.762
HR+/HER2 −
320
(17.8)
0.683
0.689
0.705 [0.616, 0.784]
HER2+
201
(46.8)
0.712
0.741
0.731 [0.658, 0.801]
TNBC
287
(43.2)
0.640
0.669
0.707 [0.646, 0.765]
TABLE IV : Receptor-subtype stratification of CoRe-WM five-fold OOF AUROC at each prospective decision point. Values are pooled out-of-fold AUROC; brackets are patient-bootstrap 95% confidence intervals.
Computer Science Department, University of Oviedo, Asturias, Spain · Biomedical Engineering Center (BME), University of Oviedo, Asturias, Spain · Electrical Engineering Department, University of Oviedo, Asturias, Spain +7