Quantifying Cross-Modal Interactions in Multimodal Glioma Survival Prediction via InterSHAP: Evidence for Additive Signal Integration

Multimodal deep learning for cancer prognosis is commonly assumed to benefit from synergistic cross-modal interactions, yet this assumption has not been directly tested in survival prediction settings. This work adapts InterSHAP, a Shapley interaction index-based metric, from classification to Cox proportional hazards models and applies it to quantify cross-modal interactions in glioma survival prediction. Using TCGA-GBM and TCGA-LGG data (n=575), we evaluate four fusion architectures combining whole-slide image (WSI) and RNA-seq features. Our central finding is an inverse relationship between predictive performance and measured interaction: architectures achieving superior discrimination (C-index 0.64$\to$0.82) exhibit equivalent or lower cross-modal interaction (4.8%$\to$3.0%). Variance decomposition reveals stable additive contributions across all architectures (WSI${\approx}$40%, RNA${\approx}$55%, Interaction${\approx}$4%), indicating that performance gains arise from complementary signal aggregation rather than learned synergy. These findings provide a practical model auditing tool for comparing fusion strategies, reframe the role of architectural complexity in multimodal fusion, and have implications for privacy-preserving federated deployment.

Source: arXiv:2603.29977v1 - http://arxiv.org/abs/2603.29977v1 PDF: https://arxiv.org/pdf/2603.29977v1 Original Link: http://arxiv.org/abs/2603.29977v1