Organizations: National University of Singapore, Singapore · Imperial College London, London, UK
Abstract
Recent multimodal survival prediction models have demonstrated strong predictive performance by leveraging complementary information across modalities. However, such models generally assume data completeness and exhibit limited robustness toward missing modalities, which are frequently encountered in real-world clinical settings. We propose the Evidential Missing Modality Survival Fusion (EMMS) model for multimodal survival prediction under missing modalities. EMMS offers a straightforward, computationally effective approach to survival analysis without requiring a generative phase for missing data. By employing Dempster-Shafer theory and Gaussian Random Fuzzy Numbers for multimodal decision fusion, it considers both aleatoric and epistemic uncertainty alongside modality reliability for fusion. Moreover, the model treats missing modalities as vacuous evidence, preventing interference with available inputs and naturally reflecting increased uncertainty and calibrated predictions. Extensive experiments on four cancer datasets demonstrate state-of-the-art performance while providing calibrated and interpretable uncertainty estimates under incomplete multimodal observations, without introducing additional computational overhead.
Multimodal fusion architectures typically assume all modalities are available at inference, yet sensor failures, acquisition variability, and cost constraints routinely produce incomplete observations. Existing work treats modality absence as a prediction-accuracy problem, leaving a more basic question unanswered: whether a model's confidence estimates remain calibrated when an entire input stream is removed. We argue that missing-modality robustness and calibrated uncertainty are a single coupled property, and introduce Modality-Conditioned Conformal Fusion (MCCF), an architecture that addresses both at once. MCCF combines a multimodal bottleneck fusion backbone trained with modality dropout, per-modality evidential heads producing modality-decomposed Dirichlet distributions, and a Dempster-Shafer combination rule that fuses the per-modality evidence into a joint predictive distribution; an absent modality contributes vacuous evidence that is structurally ignored, so the fused uncertainty automatically reflects the reduced information without test-time imputation. A Mondrian conformal calibration module keyed on the modality-presence mask then provides finite-sample group-conditional coverage for every non-empty modality subset. MCCF is, to our knowledge, the first method with formal coverage guarantees under arbitrary modality availability through architectural integration rather than post-hoc recalibration, and the evidential decomposition yields per-modality vacuity scores that localise uncertainty to the absent modality responsible. Across a synthetic problem and three real multimodal benchmarks, MCCF holds its target coverage on every modality-presence subset, substantially narrows the coverage gap between full and partial modalities relative to a marginal split-conformal baseline, and imposes no measurable accuracy cost relative to temperature-scaled and evidential baselines.
Integrating multimodal datasets in clinical oncology is frequently hindered by high dimensionality and blockwise missingness, where entire data sources are unavailable for specific patient subsets. Standard survival models often struggle with these gaps, leading to biased results or patient exclusion. We introduce Multimodality Stacking with Blockwise missing values (MSB), a late-fusion framework for survival analysis that independently models modality-specific features before aggregating predictions via a cross-validated stacking meta-learner. MSB was validated on the PIONeeR study (n=443 patients, 378 biomarkers across eight heterogeneous sources) to predict progression-free survival in advanced non-small cell lung cancer patients receiving immunotherapy. MSB yielded higher predictive performance (C-index) than baseline algorithms. Improvements varied by baseline strength: linear models showed a 15.9% increase (p<0.001 for the Wilcoxon signed-rank test), random survival forests gained 5.4% (p=0.002), and gradient boosting methods improved by 2.1% (p=0.030). Beyond discrimination, MSB reduced the generalization gap (train-test difference in 5 folds cross-validation repeated 3 times: 0.055 vs 0.380 for linear models). Permutation importance analysis identified routine laboratory markers, clinical features, and PD-L1 expression as primary predictive drivers. Missing block indicators showed negligible importance, suggesting the model learned from biomarker values rather than data availability patterns. MSB provides a statistically validated framework for multimodal survival prediction with blockwise missingness. By enabling systematic biomarker evaluation without requiring complete data, MSB offers a practical tool for predictive modeling in biomedical research, pending external validation. Implementation is available at https://github.com/MohamedBoussena/MSB under Inria license.
Mohamed Boussena, Florence Monville, Jacques Fieschi-Meric +8
We propose a novel multimodal deep learning framework for patient-level survival prediction, which integrates whole-slide histology features, RNA-seq expression profiles, and clinical variables. Our architecture combines an ABMIL module~\cite{ilse2018attention} for slide-level representation with feedforward encoders for RNA and clinical data. These embeddings are then integrated through low-rank bilinear cross-modal fusion~\cite{liu2018efficient} to model conditional interactions across modalities while controlling parameter growth. The model outputs continuous risk scores that are subsequently mapped to survival times using a nonparametric calibration procedure based on the Kaplan--Meier estimator~\cite{kaplan1958nonparametric}. By decomposing multimodal reasoning into independent pairwise interactions, the proposed fusion design promotes structural interpretability and parameter efficiency compared with full tensor and hierarchical fusion strategies. Experiments on the CHIMERA challenge dataset demonstrate improved predictive performance over concatenation-based baselines and competitive generalization on hidden evaluation cohorts. These results indicate that the proposed framework is a promising approach for multimodal survival prediction in HR-NMIBC. The implementation is publicly available at https://github.com/hassancpu/ChimeraChallenge2025_Task_3.
Hassan Keshvarikhojasteh, Josien P. W. Pluim, Mitko Veta