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Multimodal survival prediction is crucial for personalized oncology. However, existing methods typically integrate only Formalin-Fixed Paraffin-Embedded (FFPE) slides with a single omics type, such as genomics, overlooking Fresh Frozen (FF) slides that better preserve molecular information, as well as richer multi-omics data like proteomics and transcriptomics. More critically, the complete absence of certain modalities due to clinical constraints (e.g., time or cost) severely limits the applicability of conventional fusion models that rely on inter-modality correlations. To address these gaps, we propose M<sup>3</sup>Surv, a framework designed to integrate multi-pathology slides (both FF and FFPE) with multi-omics profiles. For multi-slide fusion, we design a divide-and-conquer hypergraph learning approach to capture both intra-slide higher-order cellular structures and inter-slide relationships, yielding a unified pathology representation. To enrich the biological context, we integrate multi-omics data and employ interactive cross-attention to fuse the pathological and omics modalities. To tackle the missing modality, we introduce a prototype-based memory bank. During training, this memory bank learns and stores representative pathology-omics feature prototypes. At inference, even if a modality is entirely missing, the model can query the bank with available features and robustly impute information from the most similar prototype. Extensive experiments on five TCGA cancer datasets and an in-house dataset demonstrate that M<sup>3</sup>Surv outperforms state-of-the-art methods, achieving an average 2.2% improvement in C-Index. The framework also shows strong stability across various missing modality scenarios, highlighting its clinical potential in real-world, data-incomplete scenarios.

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Publication Details

Journal
Medical Image Analysis
Published
2025-10-17
DOI
https://doi.org/10.1016/j.media.2025.103846
Primary Topic
Cancer-related molecular mechanisms research
Type
article
Field-Weighted Citation Impact
0.00
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Mingcheng Qu, Donglin Di, Yang Song, Lei Fan et al.
Medical Image Analysis
Cancer-related molecular mechanisms research
article

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Mingcheng Qu, Donglin Di, Yang Song, Lei Fan, Guang Yang, Yue Gao
article en

Abstract

Multimodal survival prediction is crucial for personalized oncology. However, existing methods typically integrate only Formalin-Fixed Paraffin-Embedded (FFPE) slides with a single omics type, such as genomics, overlooking Fresh Frozen (FF) slides that better preserve molecular information, as well as richer multi-omics data like proteomics and transcriptomics. More critically, the complete absence of certain modalities due to clinical constraints (e.g., time or cost) severely limits the applicability of conventional fusion models that rely on inter-modality correlations. To address these gaps, we propose M<sup>3</sup>Surv, a framework designed to integrate multi-pathology slides (both FF and FFPE) with multi-omics profiles. For multi-slide fusion, we design a divide-and-conquer hypergraph learning approach to capture both intra-slide higher-order cellular structures and inter-slide relationships, yielding a unified pathology representation. To enrich the biological context, we integrate multi-omics data and employ interactive cross-attention to fuse the pathological and omics modalities. To tackle the missing modality, we introduce a prototype-based memory bank. During training, this memory bank learns and stores representative pathology-omics feature prototypes. At inference, even if a modality is entirely missing, the model can query the bank with available features and robustly impute information from the most similar prototype. Extensive experiments on five TCGA cancer datasets and an in-house dataset demonstrate that M<sup>3</sup>Surv outperforms state-of-the-art methods, achieving an average 2.2% improvement in C-Index. The framework also shows strong stability across various missing modality scenarios, highlighting its clinical potential in real-world, data-incomplete scenarios.

Medical Image AnalysisVol. 107(Pt B)
Harbin Institute of Technology (CN), UNSW Sydney (AU), Tsinghua University (CN)
Openalex Percentile: Top 64%
Cancer-related molecular mechanisms research
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