Real-World Multi-Modal and Longitudinal Lung Cancer Dataset

Multimodal learning offers the potential to improve predictions by integrating complementary information from heterogeneous data sources. However, multimodal datasets are frequently incomplete, raising important questions about how models should handle missing information. Although recent approaches increasingly rely on Transformer-based architectures for multimodal fusion, incomplete multimodal data introduces challenges such as missing modalities and intra-modal missingness, which motivate key architectural design choices, such as tokenization granularity. In addition, many datasets are longitudinal, with observations collected across multiple time points. The sequential nature of the Transformer architectures provides a natural framework for modeling such data, but introduces additional considerations, such as how temporal information should be represented. In this study, we systematically investigate these design choices using three different cancer datasets. We compare modality-level and feature-level tokenization and evaluate attention masking and imputation as strategies for handling missing information, both naturally occurring in the datasets and synthetically induced. We further investigate approaches for incorporating temporal information in our training process and how to model it. Experiments are conducted with unimodal and multimodal configurations, as well as different levels of missingness for binary survival classification and multiple time encoding strategies for discrete-time survival prediction. Our results show that while multimodal outperforms unimodal results, missing data heavily impacts predictions and thus effective design choices such as tokenization granularity, and intra-missing handling is essential for reliable prediction.

Modern medicine relies on heterogeneous data sources spanning radiology, pathology, text reports, and structured clinical information. However, real-world patient data are frequently incomplete, with missing or sparsely acquired modalities, limiting the effectiveness of standard multimodal fusion approaches. To this end, we propose the Multimodal Flexible Redundancy-aware decomposed GAted Learning (Multi-FRuGaL) framework, a decomposition-aware, adaptive gated intermediate-fusion framework that performs modality-level representation learning under missing data. Multi-FRuGaL integrates per-modality encoders with a signal decomposition layer, an input-conditioned gating network, and an information-aware fusion objective to separate redundant from modality-specific complementary signals, selectively upweighting informative modalities and suppressing redundant or noisy inputs, and remaining well-defined even when multiple modalities are absent. We evaluate Multi-FRuGaL on two multimodal head and neck cancer cohorts: the HANCOCK challenge dataset (N = 763) comprising five modalities and two prognostic endpoints (5-year survival and 2-year recurrence), and the HECKTOR challenge dataset (N = 588) comprising three modalities for human papillomavirus (HPV) status classification. Multi-FRuGaL consistently achieves higher mean performance than the evaluated baselines across multiple tasks, improving AUC from 0.601 to 0.8496 for survival, from 0.672 to 0.8102 for recurrence, and achieving 0.975 AUC for HPV prediction on HECKTOR. For survival analysis, it further achieves a concordance index of 0.6814 for overall survival, 0.7421 for recurrence-free survival, and 0.7143 for progression-free survival on HANCOCK, and 0.7203 for recurrence-free survival on HECKTOR. Qualitative analyses further show that Multi-FRuGaL learns discriminative and robust multimodal representations, even under severe missing-modality conditions.

Machine learning holds promise for advancing clinical decision support, yet it remains unclear when multimodal learning truly helps in practice, particularly under modality missingness and fairness constraints. In this work, we conduct a systematic benchmark of multimodal fusion between Electronic Health Records (EHR) and chest X-rays (CXR) on standardized cohorts from MIMIC-IV and MIMIC-CXR, aiming to answer four fundamental questions: when multimodal fusion improves clinical prediction, how different fusion strategies compare, how robust existing methods are to missing modalities, and whether multimodal models achieve algorithmic fairness. Our study reveals several key insights. Multimodal fusion improves performance when modalities are complete, with gains concentrating in diseases that require complementary information from both EHR and CXR. While cross-modal learning mechanisms capture clinically meaningful dependencies beyond simple concatenation, the rich temporal structure of EHR introduces strong modality imbalance that architectural complexity alone cannot overcome. Under realistic missingness, multimodal benefits rapidly degrade unless models are explicitly designed to handle incomplete inputs. Moreover, multimodal fusion does not inherently improve fairness, with subgroup disparities mainly arising from unequal sensitivity across demographic groups. To support reproducible and extensible evaluation, we further release a flexible benchmarking toolkit that enables plug-and-play integration of new models and datasets. Together, this work provides actionable guidance on when multimodal learning helps, when it fails, and why, laying the foundation for developing clinically deployable multimodal systems that are both effective and reliable. The open-source toolkit can be found at https://github.com/jakeykj/CareBench.