Cancer Survival Prediction

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Overview

Cancer survival prediction estimates outcomes such as overall survival, recurrence, and treatment response while accounting for censored follow-up, where the event time is unknown for some patients. Methods range from Cox models and random survival forests to deep learning on pathology slides, radiology, clinical records, and genomic or other molecular data; multimodal models use attention, graphs, prototypes, or mixture-of-experts to combine these sources. Much work evaluates risk ranking on TCGA cohorts and clinical benchmarks, while handling missing modalities, learning interpretable features, and testing generalization across institutions remain central challenges. Strong concordance does not ensure accurate survival probabilities, so calibration, external validation, fairness, and robustness to data shifts also matter for clinical use.

Latest papers

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93 papers8 papers in the last four weeks, up 33% on the four weeks before. 0.0% of all new papers.

Apr 27, 2026

Benchmarking Pathology Foundation Models for Breast Cancer Survival Prediction

Pathology foundation models (PFMs) have recently emerged as powerful pretrained encoders for computational pathology, enabling transfer learning across a wide range of downstream tasks. However, systematic comparisons of these models for clinically meaningful prediction problems remain limited, especially in the context of survival prediction under external validation. In this study, we benchmark widely used and recently proposed PFMs for breast cancer survival prediction from whole-slide histopathology images. Using a standardized pipeline based on patch-level feature extraction and a unified survival modeling framework, we evaluate model representations across three independent clinical cohorts comprising more than 5,400 patients with long-term follow-up. Models are trained on one cohort and evaluated on two independent external cohorts, enabling a rigorous assessment of cross-dataset generalization. Overall, H-optimus-1 achieves the strongest survival prediction performance. More broadly, we observe consistent generational improvements across model families, with second-generation PFMs outperforming their first-generation counterparts. However, absolute performance differences between many recent PFMs remain modest, suggesting diminishing returns from further scaling of pretraining data or model size alone. Notably, the compact distilled model H0-mini slightly outperforms its larger teacher model H-optimus-0, despite using fewer than 8% of the parameters and enabling significantly faster feature extraction. Together, these results provide the first large-scale, externally validated benchmark of PFMs for breast cancer survival prediction, and offer practical guidance for efficient deployment of PFMs in clinical workflows.

Fredrik K. Gustafsson, Constance Boissin, Johan Vallon-Christersson +2

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden · Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden · Department of Engineering Science, University of Oxford, Oxford, UK +1

Cancer Survival PredictionSurvival AnalysisPathology Foundation ModelsOncologyMedical Image BenchmarksWhole-Slide Image Analysis
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Apr 27, 2026

PathMoG: A Pathway-Centric Modular Graph Neural Network for Multi-Omics Survival Prediction

Cancer survival prediction from multi-omics data remains challenging because prognostic signals are high-dimensional, heterogeneous, and distributed across interacting genes and pathways. We propose PathMoG, a pathway-centric modular graph neural network for multi-omics survival prediction. PathMoG reorganizes genome-scale inputs into 354 KEGG-informed pathway modules, introduces a Hierarchical Omics Modulation module to condition gene-expression representations on mutation, copy number variation, pathway, and clinical context, and uses dual-level attention to capture both intra-pathway driver signals and inter-pathway clinical relevance. We evaluated PathMoG on 5,650 patients across 10 TCGA cancer types and observed consistent improvements over representative survival baselines. The framework further provides gene-level, pathway-level, and patient-level interpretability, supporting biologically grounded and clinically relevant risk stratification.

Di Wang, Chupei Tang, Junxiao Kong +3

1Cuiying Honors College, Lanzhou University, China · School of Mathematics and Statistics, Lanzhou University, China · School of Mathematics and Statistics, Lanzhou University, China and Shanghai Innovation Institute +1

Survival AnalysisGraph Neural NetworksCancer Survival PredictionCancer GenomicsOncologyModular Neural Networks+1
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Apr 17, 2026

Graph Transformer-Based Pathway Embedding for Cancer Prognosis

Accurate prediction of cancer progression remains a challenge due to the high heterogeneity of molecular omics data across patients. While biologically informed models have improved the interpretability of these predictions, a persistent limitation lies in how they encode individual genes to construct pathway representations. Existing hierarchical models typically derive gene features by directly mapping raw molecular inputs, whereas integration frameworks often rely on simple statistical aggregations of patient-level signals. These approaches often fail to explicitly learn a shared base representation for each gene, thereby limiting the expressiveness and biological accuracy of downstream pathway embeddings. To address this, we introduce PATH, a modulation-based, patient-conditioned gene embedding strategy. PATH represents a paradigm shift by starting from a shared base embedding for each gene, preserving a stable biological identity across the population, and then dynamically adapting it using patient-specific copy number variation (CNV) and mutation signals. This allows the model to capture subtle individual molecular variations while maintaining a consistent latent understanding of the gene itself. We integrate PATH into a graph transformer framework that models interactions among biologically connected pathways through pathway-guided attention. Across pancancer metastasis prediction, PATH achieves an F1 score of 0.8766, representing an 8.8 percent improvement over the current SOTA multi-omics benchmarks. Beyond superior predictive accuracy, our approach identifies biologically meaningful pathways and, crucially, reveals disease-state-specific pathway rewiring, offering new insights into the evolving pathway-pathway interactions that drive cancer progression.

Koushik Howlader, Md Tauhidul Islam, Wei Le

Iowa State University, Iowa, USA · Stanford University, CA, USA

Cancer GenomicsCancer Survival PredictionClinical Outcome PredictionOncology
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Apr 17, 2026

Ranking XAI Methods for Head and Neck Cancer Outcome Prediction

For head and neck cancer (HNC) patients, prognostic outcome prediction can support personalized treatment strategy selection. Improving prediction performance of HNC outcomes has been extensively explored by using advanced artificial intelligence (AI) techniques on PET/CT data. However, the interpretability of AI remains a critical obstacle for its clinical adoption. Unlike previous HNC studies that empirically selected explainable AI (XAI) techniques, we are the first to comprehensively evaluate and rank 13 XAI methods across 24 metrics, covering faithfulness, robustness, complexity and plausibility. Experimental results on the multi-center HECKTOR challenge dataset show large variations across evaluation aspects among different XAI methods, with Integrated Gradients (IG) and DeepLIFT (DL) consistently obtained high rankings for faithfulness, complexity and plausibility. This work highlights the importance of comprehensive XAI method evaluation and can be extended to other medical imaging tasks.

Baoqiang Ma, Djennifer K. Madzia-Madzou, Rosa C. J. Kraaijveld +1

Image Sciences Institute, University Medical Center Utrecht

Gradient-Based AttributionCancer Survival PredictionOncologyExplainable Medical Image AnalysisExplainability Evaluation
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Apr 10, 2026

AMO-ENE: Attention-based Multi-Omics Fusion Model for Outcome Prediction in Extra Nodal Extension and HPV-associated Oropharyngeal Cancer

Extranodal extension (ENE) is an emerging prognostic factor in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC), although it is currently omitted as a clinical staging criteria. Recent works have advocated for the inclusion of iENE as a prognostic marker in HPV-positive OPC staging. However, several practical limitations continue to hinder its clinical integration, including inconsistencies in segmentation, low contrast in the periphery of metastatic lymph nodes on CT imaging, and laborious manual annotations. To address these limitations, we propose a fully automated end-to-end pipeline that uses computed tomography (CT) images with clinical data to assess the status of nodal ENE and predict treatment outcomes. Our approach includes a hierarchical 3D semi-supervised segmentation model designed to detect and delineate relevant iENE from radiotherapy planning CT scans. From these segmentations, a set of radiomics and deep features are extracted to train an imaging-detected ENE grading classifier. The predicted ENE status is then evaluated for its prognostic value and compared with existing staging criteria. Furthermore, we integrate these nodal features with primary tumor characteristics in a multimodal, attention-based outcome prediction model, providing a dynamic framework for outcome prediction. Our method is validated in an internal cohort of 397 HPV-positive OPC patients treated with radiation therapy or chemoradiotherapy between 2009 and 2020. For outcome prediction at the 2-year mark, our pipeline surpassed baseline models with 88.2% (4.8) in AUC for metastatic recurrence, 79.2% (7.4) for overall survival, and 78.1% (8.6) for disease-free survival. We also obtain a concordance index of 83.3% (6.5) for metastatic recurrence, 71.3% (8.9) for overall survival, and 70.0% (8.1) for disease-free survival, making it feasible for clinical decision making.

Gautier Hénique, William Le, Gabriel Dayan +8

MedICAL Laboratory, Polytechnique Montréeal, Montreal, Canada · Centre de recherche du CHUM (CRCHUM), Montréal, Canada · Centre Hospitalier de l’Université de Montréal (CHUM), Montreal Canada

Clinical Outcome PredictionCancer Survival PredictionMultimodal Survival AnalysisRadiomicsSemi-Supervised Medical Image Segmentation
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Apr 8, 2026

Time-driven Survival Analysis from FDG-PET/CT in Non-Small Cell Lung Cancer

Purpose: Automated medical image-based prediction of clinical outcomes, such as overall survival (OS), has great potential in improving patient prognostics and personalized treatment planning. We developed a deep regression framework using tissue-wise FDG-PET/CT projections as input, along with a temporal input representing a scalar time horizon (in days) to predict OS in patients with Non-Small Cell Lung Cancer (NSCLC). Methods: The proposed framework employed a ResNet-50 backbone to process input images and generate corresponding image embeddings. The embeddings were then combined with temporal data to produce OS probabilities as a function of time, effectively parameterizing the predictions based on time. The overall framework was developed using the U-CAN cohort (n = 556) and evaluated by comparing with a baseline method on the test set (n = 292). The baseline utilized the ResNet-50 architecture, processing only the images as input and providing OS predictions at pre-specified intervals, such as 2- or 5-year. Results: The incorporation of temporal data with image embeddings demonstrated an advantage in predicting OS, outperforming the baseline method with an improvement in AUC of 4.3%. The proposed model using clinical + IDP features achieved strong performance, and an ensemble of imaging and clinical + IDP models achieved the best overall performance (0.788), highlighting the complementary value of multimodal inputs. The proposed method also enabled risk stratification of patients into distinct categories (high vs low risk). Heat maps from the saliency analysis highlighted tumor regions as key structures for the prediction. Conclusion: Our method provided an automated framework for predicting OS as a function of time and demonstrates the potential of combining imaging and tabular data for improved survival prediction.

Sambit Tarai, Ashish Chauhan, Elin Lundström +5

Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, SE-75185, Sweden · Molecular Imaging and Medical Physics, Department of Surgical Sciences, Uppsala University, Uppsala, SE-75185, Sweden · Antaros Medical, Mölndal, SE-43153, Sweden

Cancer Survival PredictionSurvival AnalysisMultimodal Survival Analysis
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Apr 7, 2026

MorphDistill: Distilling Unified Morphological Knowledge from Pathology Foundation Models for Colorectal Cancer Survival Prediction

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Accurate survival prediction is essential for treatment stratification, yet existing pathology foundation models often overlook organ-specific features critical for CRC prognostication. Methods: We propose MorphDistill, a two-stage framework that distills complementary knowledge from multiple pathology foundation models into a compact CRC-specific encoder. In Stage I, a student encoder is trained using dimension-agnostic multi-teacher relational distillation with supervised contrastive regularization on large-scale colorectal datasets. This preserves inter-sample relationships from ten foundation models without explicit feature alignment. In Stage II, the encoder extracts patch-level features from whole-slide images, which are aggregated via attention-based multiple instance learning to predict five-year survival. Results: On the Alliance/CALGB 89803 cohort (n=424, stage III CRC), MorphDistill achieves an AUC of 0.68 (SD 0.08), an approximately 8% relative improvement over the strongest baseline (AUC 0.63). It also attains a C-index of 0.661 and a hazard ratio of 2.52 (95% CI: 1.73-3.65), outperforming all baselines. On an external TCGA cohort (n=562), it achieves a C-index of 0.628, demonstrating strong generalization across datasets and robustness across clinical subgroups. Conclusion: MorphDistill enables task-specific representation learning by integrating knowledge from multiple foundation models into a unified encoder. This approach provides an efficient strategy for prognostic modeling in computational pathology, with potential for broader oncology applications. Further validation across additional cohorts and disease stages is warranted.

Hikmat Khan, Usama Sajjad, Metin N. Gurcan +4

Department of Pathology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA · Center for Artificial Intelligence Research, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA

Cancer Survival PredictionComputational PathologyMedical Image Representation LearningPathology Foundation Models
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Apr 7, 2026

MO-RiskVAE: A Multi-Omics Variational Autoencoder for Survival Risk Modeling in Multiple MyelomaMO-RiskVAE

Multimodal variational autoencoders (VAEs) have emerged as a powerful framework for survival risk modeling in multiple myeloma by integrating heterogeneous omics and clinical data. However, when trained under survival supervision, standard latent regularization strategies often fail to preserve prognostically relevant variation, leading to unstable or overly constrained representations. Despite numerous proposed variants, it remains unclear which aspects of latent design fundamentally govern performance in this setting. In this work, we conduct a controlled investigation of latent modeling choices for multimodal survival prediction within a unified extension of the MyeVAE framework. By systematically isolating regularization scale, posterior geometry, and latent space structure under identical architectures and optimization protocols, we show that survival-driven training is primarily sensitive to the magnitude and structure of latent regularization rather than the specific divergence formulation. In particular, moderate relaxation of KL regularization consistently improves survival discrimination, while alternative divergence mechanisms such as MMD and HSIC provide limited benefit without appropriate scaling. We further demonstrate that structuring the latent space can improve alignment between learned representations and survival risk gradients. A hybrid continuous--discrete formulation based on Gumbel--Softmax enhances global risk ordering in the continuous latent subspace, even though stable discrete subtype discovery does not emerge under survival supervision. Guided by these findings, we instantiate a robust multimodal survival model, termed MO-RiskVAE, which consistently improves risk stratification over the original MyeVAE without introducing additional supervision or complex training heuristics.

Zixuan Chen, Heng Zhang, YuPeng Qin +5

Binjiang Institute of Zhejiang University · Zhejiang University · School of Medicine, Zhejiang University

Latent-Space RegularizationCancer Survival PredictionMultimodal Survival AnalysisVariational Autoencoders
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Apr 5, 2026

PRIME: Prototype-Driven Multimodal Pretraining for Cancer Prognosis with Missing Modalities

Multimodal self-supervised pretraining offers a promising route to cancer prognosis by integrating histopathology whole-slide images, gene expression, and pathology reports, yet most existing approaches require fully paired and complete inputs. In practice, clinical cohorts are fragmented and often miss one or more modalities, limiting both supervised fusion and scalable multimodal pretraining. We propose PRIME, a missing-aware multimodal self-supervised pretraining framework that learns robust and transferable representations from partially observed cohorts. PRIME maps heterogeneous modality embeddings into a unified token space and introduces a shared prototype memory bank for latent-space semantic imputation via patient-level consensus retrieval, producing structurally aligned tokens without reconstructing raw signals. Two complementary pretraining objectives: inter-modality alignment and post-fusion consistency under structured missingness augmentation, jointly learn representations that remain predictive under arbitrary modality subsets. We evaluate PRIME on The Cancer Genome Atlas with label-free pretraining on 32 cancer types and downstream 5-fold evaluation on five cohorts across overall survival prediction, 3-year mortality classification, and 3-year recurrence classification. PRIME achieves the best macro-average performance among all compared methods, reaching 0.653 C-index, 0.689 AUROC, and 0.637 AUROC on the three tasks, respectively, while improving robustness under test-time missingness and supporting parameter-efficient and label-efficient adaptation. These results support missing-aware multimodal pretraining as a practical strategy for prognosis modeling in fragmented clinical data settings.

Kai Yu, Shuang Zhou, Yiran Song +9

Division of Computational Health Sciences, Department of Surgery, University of Minnesota, Minneapolis, MN, USA. · University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · North Carolina State University, Raleigh, NC, USA. +2

Multimodal PretrainingMissing-Modality LearningSelf-Supervised Pre-TrainingCancer Survival PredictionIncomplete Data Imputation
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Apr 5, 2026

Good Rankings, Wrong Probabilities: A Calibration Audit of Multimodal Cancer Survival Models

Multimodal deep learning models that fuse whole-slide histopathology images with genomic data have achieved strong discriminative performance for cancer survival prediction, as measured by the concordance index. Yet whether the survival probabilities derived from these models - either directly from native outputs or via standard post-hoc reconstruction - are calibrated remains largely unexamined. We conduct, to our knowledge, the first systematic fold-level 1-calibration audit of multimodal WSI-genomics survival architectures, evaluating native discrete-time survival outputs (Experiment A: 3 models on TCGA-BRCA) and Breslow-reconstructed survival curves from scalar risk scores (Experiment B: 11 architectures across 5 TCGA cancer types). In Experiment A, all three models fail 1-calibration on a majority of folds (12 of 15 fold-level tests reject after Benjamini-Hochberg correction). Across the full 290 fold-level tests, 166 reject the null of correct calibration at the median event time after Benjamini-Hochberg correction (FDR = 0.05). MCAT achieves C-index 0.817 on GBMLGG yet fails 1-calibration on all five folds. Gating-based fusion is associated with better calibration; bilinear and concatenation fusion are not. Post-hoc Platt scaling reduces miscalibration at the evaluated horizon (e.g., MCAT: 5/5 folds failing to 2/5) without affecting discrimination. The concordance index alone is insufficient for evaluating survival models intended for clinical use.

Sajad Ghawami

Independent Researcher

Cancer Survival PredictionMultimodal Survival AnalysisSurvival AnalysisPost-Hoc CalibrationMultimodal Fusion
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Mar 31, 2026

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→\to0.82) exhibit equivalent or lower cross-modal interaction (4.8%→\to3.0%). 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.

Iain Swift, JingHua Ye, Ruairi O'Reilly

Department of Computer Science, Munster Technological University, Cork, Ireland

Multimodal FusionMultimodal Survival AnalysisCancer Survival PredictionMultimodal Model InterpretabilityShapley Value Attribution
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Mar 31, 2026

Trimodal Deep Learning for Glioma Survival Prediction: A Feasibility Study Integrating Histopathology, Gene Expression, and MRI

Multimodal deep learning has improved prognostic accuracy for brain tumours by integrating histopathology and genomic data, yet the contribution of volumetric MRI within unified survival frameworks remains unexplored. This pilot study extends a bimodal framework by incorporating Fluid Attenuated Inversion Recovery (FLAIR) MRI from BraTS2021 as a third modality. Using the TCGA-GBMLGG cohort (664 patients), we evaluate three unimodal models, nine bimodal configurations, and three trimodal configurations across early, late, and joint fusion strategies. In this small cohort setting, trimodal early fusion achieves an exploratory Composite Score (CS = 0.854), with a controlled ΔΔCS of +0.011 over the bimodal baseline on identical patients, though this difference is not statistically significant (p = 0.250, permutation test). MRI achieves reasonable unimodal discrimination (CS = 0.755) but does not substantially improve bimodal pairs, while providing measurable uplift in the three-way combination. All MRI containing experiments are constrained to 19 test patients, yielding wide bootstrap confidence intervals (e.g. [0.400,1.000]) that preclude definitive conclusions. These findings provide preliminary evidence that a third imaging modality may add prognostic value even with limited sample sizes, and that additional modalities require sufficient multimodal context to contribute effectively.

Iain Swift, JingHua Ye

Department of Computer Science, Munster Technological University, Cork, Ireland

Cancer Survival PredictionMultimodal Survival AnalysisMultimodal Fusion
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Mar 31, 2026

Genetic algorithms for multi-omic feature selection: a comparative study in cancer survival analysis

Multi-omic datasets offer opportunities for improved biomarker discovery in cancer research, but their high dimensionality and limited sample sizes make identifying compact and effective biomarker panels challenging. Feature selection in large-scale omics can be efficiently addressed by combining machine learning with genetic algorithms, which naturally support multi-objective optimization of predictive accuracy and biomarker set size. However, genetic algorithms remain relatively underexplored for multi-omic feature selection, where most approaches concatenate all layers into a single feature space. To address this limitation, we introduce Sweeping*, a multi-view, multi-objective algorithm alternating between single- and multi-view optimization. It employs a nested single-view multi-objective optimizer, and for this study we use the genetic algorithm NSGA3-CHS. It first identifies informative biomarkers within each layer, then jointly evaluates cross-layer interactions; these multi-omic solutions guide the next single-view search. Through repeated sweeps, the algorithm progressively identifies compact biomarker panels capturing cross-modal complementary signals. We benchmark five Sweeping* strategies, including hierarchical and concatenation-based variants, using survival prediction on three TCGA cohorts. Each strategy jointly optimizes predictive accuracy and set size, measured via the concordance index and root-leanness. Overall performance and estimation error are assessed through cross hypervolume and Pareto delta under 5-fold cross-validation. Our results show that Sweeping* can improve the accuracy-complexity trade-off when sufficient survival signal is present and that integrating omic layers can enhance survival prediction beyond clinical-only models, although benefits remain cohort-dependent.

Luca Cattelani, Vittorio Fortino

Institute of Biomedicine, School of Medicine, University of Eastern Finland, Yliopistonranta 8, 70210, Finland

Feature SelectionGenetic AlgorithmsMulti-Omics Data IntegrationMulti-Objective Evolutionary OptimizationCancer Survival Prediction
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Mar 28, 2026

Pan-Cancer Mapping of the Tumor Immune Landscape through Metagene Clustering and Predictive Modeling

As immunotherapies become standard cancer treatments, it is increasingly important to identify a patient's immune profile, which encompasses the activity of immune cells within the tumor microenvironment and the presence of specific biomarkers. However, we lack mechanistic explanations drivers of immune phenotypes. Despite advances in immune profiling with high-throughput sequencing, the mechanisms driving them remain unclear. This study aimed to identify novel, robust immune-related gene clusters (metagenes) and evaluate their prognostic significance and functional relevance across various pan-cancer types using a comprehensive computational pipeline. We acquired pan-cancer bulk RNA-seq and established immune subtypes from The Cancer Genome Atlas (TCGA). Using expression-based filtering and clustering of genes with ANOVA and Gaussian Mixture Model (GMM), we identified 48 unique metagenes. These metagenes achieved 87% accuracy in predicting the established subtypes. SHAP analysis revealed the most predictive metagenes per subtype, while functional enrichment analysis identified their associated pathways. Genes were ranked by differential expression between high- and low-expression groups. The metagenes revealed insights, including co-expression of immune activation and regulatory factors, links between cell cycle regulation and immune evasion, and dynamic microenvironment remodeling signatures. Kaplan-Meier survival analysis and multivariate Cox Regression revealed that many metagenes had prognostic value for overall survival. Overall, the metagenes represent coordinated biological programs across diverse cancer types, providing a foundation for developing robust, broadly applicable immuno-oncology biomarkers that extend beyond single-gene markers. They demonstrate prognostic value across cancer types and hold potential to guide immunotherapy treatment decisions.

Soham Chatterjee

Cancer Subtype ClassificationOncologyCancer GenomicsCancer Survival Prediction
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Mar 27, 2026

MUST: Modality-Specific Representation-Aware Transformer for Diffusion-Enhanced Survival Prediction with Missing Modality

Accurate survival prediction from multimodal medical data is essential for precision oncology, yet clinical deployment faces a persistent challenge: modalities are frequently incomplete due to cost constraints, technical limitations, or retrospective data availability. While recent methods attempt to address missing modalities through feature alignment or joint distribution learning, they fundamentally lack explicit modeling of the unique contributions of each modality as opposed to the information derivable from other modalities. We propose MUST (Modality-Specific representation-aware Transformer), a novel framework that explicitly decomposes each modality's representation into modality-specific and cross-modal contextualized components through algebraic constraints in a learned low-rank shared subspace. This decomposition enables precise identification of what information is lost when a modality is absent. For the truly modality-specific information that cannot be inferred from available modalities, we employ conditional latent diffusion models to generate high-quality representations conditioned on recovered shared information and learned structural priors. Extensive experiments on five TCGA cancer datasets demonstrate that MUST achieves state-of-the-art performance with complete data while maintaining robust predictions in both missing pathology and missing genomics conditions, with clinically acceptable inference latency.

Kyungwon Kim, Dosik Hwang

Yonsei University · Korea Institute of Science and Technology

Multimodal Survival AnalysisMissing-Modality LearningCancer Survival PredictionRepresentation LearningMultimodal Diffusion Models
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Mar 23, 2026

Multimodal Survival Analysis with Locally Deployable Large Language Models

We study multimodal survival analysis integrating clinical text, tabular covariates, and genomic profiles using locally deployable large language models (LLMs). As many institutions face tight computational and privacy constraints, this setting motivates the use of lightweight, on-premises models. Our approach jointly estimates calibrated survival probabilities and generates concise, evidence-grounded prognosis text via teacher-student distillation and principled multimodal fusion. On a TCGA cohort, it outperforms standard baselines, avoids reliance on cloud services and associated privacy concerns, and reduces the risk of hallucinated or miscalibrated estimates that can be observed in base LLMs.

Moritz Gögl, Christopher Yau

University of Oxford

Multimodal Survival AnalysisCancer Survival PredictionMedical LLMs
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Mar 20, 2026

Interpretable Multiple Myeloma Prognosis with Observational Medical Outcomes Partnership Data

Machine learning (ML) promises better clinical decision-making, yet opaque model behavior limits the adoption in healthcare. We propose two novel regularization techniques for ensuring the interpretability of ML models trained on real-world data. In particular, we consider the prediction of five-year survival for multiple myeloma patients using clinical data from Helsinki University Hospital. To ensure the interpretability of the trained models, we use two alternative constructions for a penalty term used for regularization. The first one penalizes deviations from the predictions obtained from an interpretable logistic regression method with two manually chosen features. The second construction requires consistency of model predictions with the revised international staging system (R-ISS). We verify the usefulness of the proposed regularization techniques in numerical experiments using data from 812 patients. They achieve an accuracy up to 0.721 on a test set and SHAP values show that the models rely on the selected important features.

Salma Rachidi, Aso Bozorgpanah, Eric Fey +1

Aalto University, Dept. of Computer Science, Espoo, Finland · Helsinki University Hospital, Helsinki, Finland

Interpretable MLCancer Survival Prediction
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Mar 17, 2026

HistoAtlas: A Pan-Cancer Morphology Atlas Linking Histomics to Molecular Programs and Clinical Outcomes

We present HistoAtlas, a pan-cancer computational atlas that extracts 38 interpretable histomic features from 6,745 diagnostic H&E slides across 21 TCGA cancer types and systematically links every feature to survival, gene expression, somatic mutations, and immune subtypes. All associations are covariate-adjusted, multiple-testing corrected, and classified into evidence-strength tiers. The atlas recovers known biology, from immune infiltration and prognosis to proliferation and kinase signaling, while uncovering compartment-specific immune signals and morphological subtypes with divergent outcomes. Every result is spatially traceable to tissue compartments and individual cells, statistically calibrated, and openly queryable. HistoAtlas enables systematic, large-scale biomarker discovery from routine H&E without specialized staining or sequencing. Data and an interactive web atlas are freely available at https://histoatlas.com .

Pierre-Antoine Bannier

Computational PathologyWhole-Slide Image AnalysisCancer Survival PredictionScientific Discovery
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Mar 17, 2026

HGP-Mamba: Integrating Histology and Generated Protein Features for Mamba-based Multimodal Survival Risk Prediction

Recent advances in multimodal learning have significantly improved cancer survival risk prediction. However, the joint prognostic potential of protein markers and histopathology images remains underexplored, largely due to the high cost and limited availability of protein expression profiling. To address this challenge, we propose HGP-Mamba, a Mamba-based multimodal framework that efficiently integrates histological with generated protein features for survival risk prediction. Specifically, we introduce a protein feature extractor (PFE) that leverages pretrained foundation models to derive high-throughput protein embeddings directly from Whole Slide Images (WSIs), enabling data-efficient incorporation of molecular information. Together with histology embeddings that capture morphological patterns, we further introduce the Local Interaction-aware Mamba (LiAM) for fine-grained feature interaction and the Global Interaction-enhanced Mamba (GiEM) to promote holistic modality fusion at the slide level, thus capture complex cross-modal dependencies. Experiments on four public cancer datasets demonstrate that HGP-Mamba achieves state-of-the-art performance while maintaining superior computational efficiency compared with existing methods. Our source code is publicly available at https://github.com/Daijing-ai/HGP-Mamba.git.

Jing Dai, Chen Wu, Ming Wu +4

Cancer Hospital of Dalian University of Technology, Shenyang, China · School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, China · Key Laboratory of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian, China

Cancer Survival PredictionMultimodal Survival AnalysisComputational PathologyMultimodal FusionWhole-Slide Image AnalysisState Space Models
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Mar 15, 2026

Deep Learning From Routine Histology Improves Risk Stratification for Biochemical Recurrence in Prostate Cancer

Accurate prediction of biochemical recurrence (BCR) after radical prostatectomy is critical for guiding adjuvant treatment and surveillance decisions in prostate cancer. However, existing clinicopathological risk models reduce complex morphology to relatively coarse descriptors, leaving substantial prognostic information embedded in routine histopathology underexplored. We present a deep learning-based biomarker that predicts continuous, patient-specific risk of BCR directly from H&E-stained whole-slide prostatectomy specimens. Trained end-to-end on time-to-event outcomes and evaluated across four independent international cohorts, our model demonstrates robust generalization across institutions and patient populations. When integrated with the CAPRA-S clinical risk score, the deep learning risk score consistently improved discrimination for BCR, increasing concordance indices from 0.725-0.772 to 0.749-0.788 across cohorts. To support clinical interpretability, outcome-grounded analyses revealed subtle histomorphological patterns associated with recurrence risk that are not captured by conventional clinicopathological risk scores. This multicohort study demonstrates that deep learning applied to routine prostate histopathology can deliver reproducible and clinically generalizable biomarkers that augment postoperative risk stratification, with potential to support personalized management of prostate cancer in real-world clinical settings.

Clément Grisi, Khrystyna Faryna, Nefise Uysal +11

Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands · Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy · Surgical Pathology Unit, Verona University Hospital Trust, Verona, Italy +4

Clinical Risk PredictionOncologyCancer Survival PredictionComputational Pathology
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Mar 14, 2026

Advancing Cancer Prognosis with Hierarchical Fusion of Genomic, Proteomic and Pathology Imaging Data from a Systems Biology Perspective

To enhance the precision of cancer prognosis, recent research has increasingly focused on multimodal survival methods by integrating genomic data and histology images. However, current approaches overlook the fact that the proteome serves as an intermediate layer bridging genomic alterations and histopathological features while providing complementary biological information essential for survival prediction. This biological reality exposes another architectural limitation: existing integrative analysis studies fuse these heterogeneous data sources in a flat manner that fails to capture their inherent biological hierarchy. To address these limitations, we propose HFGPI, a hierarchical fusion framework that models the biological progression from genes to proteins to histology images from a systems biology perspective. Specifically, we introduce Molecular Tokenizer, a molecular encoding strategy that integrates identity embeddings with expression profiles to construct biologically informed representations for genes and proteins. We then develop Gene-Regulated Protein Fusion (GRPF), which employs graph-aware cross-attention with structure-preserving alignment to explicitly model gene-protein regulatory relationships and generate gene-regulated protein representations. Additionally, we propose Protein-Guided Hypergraph Learning (PGHL), which establishes associations between proteins and image patches, leveraging hypergraph convolution to capture higher-order protein-morphology relationships. The final features are progressively fused across hierarchical layers to achieve precise survival outcome prediction. Extensive experiments on five benchmark datasets demonstrate the superiority of HFGPI over state-of-the-art methods.

Junjie Zhou, Bao Xue, Meiling Wang +2

The College of Artificial Intelligence, Nanjing University of Aeronautics and Astronautics · School of Computer Science, Nanjing University of Posts and Telecommunications

Cancer Survival PredictionMultimodal Survival AnalysisMultimodal FusionComputational Pathology
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Mar 12, 2026

Leveraging Large Language Models and Survival Analysis for Early Prediction of Chemotherapy Outcomes

Chemotherapy for cancer treatment is costly and accompanied by severe side effects, highlighting the critical need for early prediction of treatment outcomes to improve patient management and informed decision-making. Predictive models for chemotherapy outcomes using real-world data face challenges, including the absence of explicit phenotypes and treatment outcome labels such as cancer progression and toxicity. This study addresses these challenges by employing Large Language Models (LLMs) and ontology-based techniques for phenotypes and outcome label extraction from patient notes. We focused on one of the most frequently occurring cancers, breast cancer, due to its high prevalence and significant variability in patient response to treatment, making it a critical area for improving predictive modeling. The dataset included features such as vitals, demographics, staging, biomarkers, and performance scales. Drug regimens and their combinations were extracted from the chemotherapy plans in the EMR data and shortlisted based on NCCN guidelines, verified with NIH standards, and analyzed through survival modeling. The proposed approach significantly reduced phenotypes sparsity and improved predictive accuracy. Random Survival Forest was used to predict time-to-failure, achieving a C-index of 73%, and utilized as a classifier at a specific time point to predict treatment outcomes, with accuracy and F1 scores above 70%. The outcome probabilities were validated for reliability by calibration curves. We extended our approach to four other cancer types. This research highlights the potential of early prediction of treatment outcomes using LLM-based clinical data extraction enabling personalized treatment plans with better patient outcomes.

Muhammad Faisal Shahid, Asad Afzal, Abdullah Faiz +5

CureMD Research, 80 Pine St 21st Floor, New York, NY 10005, United States

Clinical Outcome PredictionCancer Survival PredictionBreast Cancer
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Mar 11, 2026

Sparse Task Vector Mixup with Hypernetworks for Efficient Knowledge Transfer in Whole-Slide Image Prognosis

Whole-Slide Images (WSIs) are widely used for estimating the prognosis of cancer patients. Current studies generally follow a cancer-specific learning paradigm. However, the available training samples for one cancer type are usually scarce in pathology. Consequently, the model often struggles to learn generalizable knowledge, thus performing worse on the tumor samples with inherent high heterogeneity. Although multi-cancer joint learning and knowledge transfer approaches have been explored recently to address it, they either rely on large-scale joint training or extensive inference across multiple models, posing new challenges in computational efficiency. To this end, this paper proposes a new scheme, Sparse Task Vector Mixup with Hypernetworks (STEPH). Unlike previous ones, it efficiently absorbs generalizable knowledge from other cancers for the target via model merging: i) applying task vector mixup to each source-target pair and then ii) sparsely aggregating task vector mixtures to obtain an improved target model, driven by hypernetworks. Extensive experiments on 13 cancer datasets show that STEPH improves over cancer-specific learning and an existing knowledge transfer baseline by 5.14% and 2.01%, respectively. Moreover, it is a more efficient solution for learning prognostic knowledge from other cancers, without requiring large-scale joint training or extensive multi-model inference. Code is publicly available at https://github.com/liupei101/STEPH.

Pei Liu, Xiangxiang Zeng, Tengfei Ma +3

College of Computer Science and Electronic Engineering, Hunan University · National University of Singapore

Whole-Slide Image AnalysisCancer Survival PredictionCross-Domain Transfer LearningModel Merging
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Mar 10, 2026

An Automated Radiomics Framework for Postoperative Survival Prediction in Colorectal Liver Metastases using Preoperative MRI

While colorectal liver metastasis (CRLM) is potentially curable via hepatectomy, patient outcomes remain highly heterogeneous. Postoperative survival prediction is necessary to avoid non-beneficial surgeries and guide personalized therapy. In this study, we present an automated AI-based framework for postoperative CRLM survival prediction using pre- and post-contrast MRI. We performed a retrospective study of 227 CRLM patients who had gadoxetate-enhanced MRI prior to curative-intent hepatectomy between 2013 and 2020. We developed a survival prediction framework comprising an anatomy-aware segmentation pipeline followed by a radiomics pipeline. The segmentation pipeline learns liver, CRLMs, and spleen segmentation from partially-annotated data, leveraging promptable foundation models to generate pseudo-labels. To support this pipeline, we propose SAMONAI, a prompt propagation algorithm that extends Segment Anything Model to 3D point-based segmentation. Predicted pre- and post-contrast segmentations are then fed into our radiomics pipeline, which extracts per-tumor features and predicts survival using SurvAMINN, an autoencoder-based multiple instance neural network for time-to-event survival prediction. SurvAMINN jointly learns dimensionality reduction and survival prediction from right-censored data, emphasizing high-risk metastases. We compared our framework against established methods and biomarkers using univariate and multivariate Cox regression. Our segmentation pipeline achieves median Dice scores of 0.96 (liver) and 0.93 (spleen), driving a CRLM segmentation Dice score of 0.78 and a detection F1-score of 0.79. Accurate segmentation enables our radiomics pipeline to achieve a survival prediction C-index of 0.69. Our results show the potential of integrating segmentation algorithms with radiomics-based survival analysis to deliver accurate and automated CRLM outcome prediction.

Muhammad Alberb, Jianan Chen, Hossam El-rewaidy +5

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada · Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada · UCL Cancer Institute, University College London, London, UK +5

Cancer Survival PredictionRadiomicsSurvival AnalysisMedical Image SegmentationSemi-Supervised Medical Image Segmentation
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Mar 2, 2026

Bridging the gap between Performance and Interpretability: An Explainable Disentangled Multimodal Framework for Cancer Survival Prediction

While multimodal survival prediction models are increasingly more accurate, their complexity often reduces interpretability, limiting insight into how different data sources influence predictions. To address this, we introduce DIMAFx, an explainable multimodal framework for cancer survival prediction that produces disentangled, interpretable modality-specific and modality-shared representations from histopathology whole-slide images and transcriptomics data. Across multiple cancer cohorts, DIMAFx achieves state-of-the-art performance and improved representation disentanglement. Leveraging its interpretable design and SHapley Additive exPlanations, DIMAFx systematically reveals key multimodal interactions and the biological information encoded in the disentangled representations. In breast cancer survival prediction, the most predictive features contain modality-shared information, including one capturing solid tumor morphology contextualized primarily by late estrogen response, where higher-grade morphology aligned with pathway upregulation and increased risk, consistent with known breast cancer biology. Key modality-specific features capture microenvironmental signals from interacting adipose and stromal morphologies. These results show that multimodal models can overcome the traditional trade-off between performance and explainability, supporting their application in precision medicine.

Aniek Eijpe, Soufyan Lakbir, Melis Erdal Cesur +4

AI Technology for Life, Department of Information and Computing Sciences, Department of Biology, Utrecht University, Utrecht, The Netherlands · Department of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands · Regenerative Medicine Center Utrecht, Utrecht, The Netherlands +3

Cancer Survival PredictionMultimodal Survival AnalysisMultimodal Model InterpretabilityMultimodal Disentangled Representation LearningComputational Pathology
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Feb 26, 2026

Hierarchical Multi-Scale Graph Learning with Knowledge-Guided Attention for Whole-Slide Image Survival Analysis

We propose a Hierarchical Multi-scale Knowledge-aware Graph Network (HMKGN) that models multi-scale interactions and spatially hierarchical relationships within whole-slide images (WSIs) for cancer prognostication. Unlike conventional attention-based MIL, which ignores spatial organization, or graph-based MIL, which relies on static handcrafted graphs, HMKGN enforces a hierarchical structure with spatial locality constraints, wherein local cellular-level dynamic graphs aggregate spatially proximate patches within each region of interest (ROI) and a global slide-level dynamic graph integrates ROI-level features into WSI-level representations. Moreover, multi-scale integration at the ROI level combines coarse contextual features from broader views with fine-grained structural representations from local patch-graph aggregation. We evaluate HMKGN on four TCGA cohorts (KIRC, LGG, PAAD, and STAD; N=513, 487, 138, and 370) for survival prediction. It consistently outperforms existing MIL-based models, yielding improved concordance indices (10.85% better) and statistically significant stratification of patient survival risk (log-rank p < 0.05).

Bin Xu, Yufei Zhou, Boling Song +6

Nanjing University of Information Science and Technology, Nanjing, China · Case Western Reserve University, Cleveland, OH, USA · Georgia Institute of Technology and Emory University, Atlanta, GA, USA +4

Hierarchical GNNsCancer Survival PredictionWhole-Slide Image AnalysisComputational PathologyMulti-Scale Feature Fusion
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Feb 25, 2026

Multimodal Survival Modeling and Fairness-Aware Clinical Machine Learning for 5-Year Breast Cancer Risk Prediction

Clinical risk prediction models often underperform in real-world settings due to poor calibration, limited transportability, and subgroup disparities. These challenges are amplified in high-dimensional multimodal cancer datasets characterized by complex feature interactions and a p >> n structure. We present a fully reproducible multimodal machine learning framework for 5-year overall survival prediction in breast cancer, integrating clinical variables with high-dimensional transcriptomic and copy-number alteration (CNA) features from the METABRIC cohort. After variance- and sparsity-based filtering and dimensionality reduction, models were trained using stratified train/validation/test splits with validation-based hyperparameter tuning. Two survival approaches were compared: an elastic-net regularized Cox model (CoxNet) and a gradient-boosted survival tree model implemented using XGBoost. CoxNet provides embedded feature selection and stable estimation, whereas XGBoost captures nonlinear effects and higher-order interactions. Performance was assessed using time-dependent area under the ROC curve (AUC), average precision (AP), calibration curves, Brier score, and bootstrapped 95 percent confidence intervals. CoxNet achieved validation and test AUCs of 98.3 and 96.6, with AP values of 90.1 and 80.4. XGBoost achieved validation and test AUCs of 98.6 and 92.5, with AP values of 92.5 and 79.9. Fairness diagnostics showed stable discrimination across age groups, estrogen receptor status, molecular subtypes, and menopausal state. This work introduces a governance-oriented multimodal survival framework emphasizing calibration, fairness auditing, robustness, and reproducibility for high-dimensional clinical machine learning.

Toktam Khatibi

Faculty of Industrial and Systems Engineering, Tarbiat Modares University, Tehran, Iran

Cancer Survival PredictionMultimodal Survival AnalysisSurvival AnalysisBreast Cancer
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Feb 23, 2026

Counterfactual Understanding via Retrieval-aware Multimodal Modeling for Time-to-Event Survival Prediction

This paper tackles the problem of time-to-event counterfactual survival prediction, aiming to optimize individualized survival outcomes in the presence of heterogeneity and censored data. We propose CURE, a framework that advances counterfactual survival modeling via comprehensive multimodal embedding and latent subgroup retrieval. CURE integrates clinical, paraclinical, demographic, and multi-omics information, which are aligned and fused through cross-attention mechanisms. Complex multi-omics signals can be adaptively refined using a mixture-of-experts architecture, emphasizing the most informative omics components. Building upon this representation, CURE implicitly retrieves patient-specific latent subgroups that capture both baseline survival dynamics and treatment-dependent variations. Experimental results on METABRIC and TCGA-LUAD datasets demonstrate that proposed CURE model consistently outperforms strong baselines in survival analysis, evaluated using the Time-dependent Concordance Index (CtdC^{td}) and Integrated Brier Score (IBS). These findings highlight the potential of CURE to enhance multimodal understanding and serve as a foundation for future treatment recommendation models. All code and related resources are publicly available to facilitate the reproducibility https://github.com/L2R-UET/CURE.

Ha-Anh Hoang Nguyen, Tri-Duc Phan Le, Duc-Hoang Pham +4

University of Engineering and Technology, Hanoi Vietnam National University, Vietnam · Delft University of Technology, the Netherlands

Counterfactual PredictionCancer Survival PredictionCounterfactual LearningMultimodal Survival Analysis
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Feb 19, 2026

A Contrastive Variational AutoEncoder for NSCLC Survival Prediction with Missing Modalities

Predicting survival outcomes for non-small cell lung cancer (NSCLC) patients is challenging due to the different individual prognostic features. This task can benefit from the integration of whole-slide images, bulk transcriptomics, and DNA methylation, which offer complementary views of the patient's condition at diagnosis. However, real-world clinical datasets are often incomplete, with entire modalities missing for a significant fraction of patients. State-of-the-art models rely on available data to create patient-level representations or use generative models to infer missing modalities, but they lack robustness in cases of severe missingness. We propose a Multimodal Contrastive Variational AutoEncoder (MCVAE) to address this issue: modality-specific variational encoders capture the uncertainty in each data source, and a fusion bottleneck with learned gating mechanisms is introduced to normalize the contributions from present modalities. We propose a multi-task objective that combines survival loss and reconstruction loss to regularize patient representations, along with a cross-modal contrastive loss that enforces cross-modal alignment in the latent space. During training, we apply stochastic modality masking to improve the robustness to arbitrary missingness patterns. Extensive evaluations on the TCGA-LUAD (n=475) and TCGA-LUSC (n=446) datasets demonstrate the efficacy of our approach in predicting disease-specific survival (DSS) and its robustness to severe missingness scenarios compared to two state-of-the-art models. Finally, we bring some clarifications on multimodal integration by testing our model on all subsets of modalities, finding that integration is not always beneficial to the task.

Michele Zanitti, Vanja Miskovic, Francesco Trovò +5

Department of Electronic Systems, Aalborg University, Copenhagen, Denmark · Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy · Department of Medical Oncology, Istituto Nazionale dei Tumori, Milan, Italy

Cancer Survival PredictionMultimodal Survival AnalysisMissing-Modality LearningMultimodal Contrastive LearningConditional Variational Autoencoder
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Nov 22, 2025

Together, Then Apart: Balancing Alignment and Distinctiveness for Multimodal Survival Analysis

Multimodal survival analysis aims to improve cancer prognosis using heterogeneous biomedical data, such as histopathology images and genomic profiles. A common strategy is to align representations across modalities so that shared signals can be captured. However, strong cross-modal alignment can also remove modality-specific evidence that is critical for survival prediction. In this paper, we revisit multimodal survival learning from a simple observation: effective models should first discover shared patterns across modalities, and then preserve modality-specific signals. This motivates a representation learning principle that we refer to as Together Then Apart. Based on this idea, we propose TTA, a framework that balances cross-modal alignment and representation distinctiveness. TTA first performs prototype-based alignment to capture shared survival-related structures between modalities. It then encourages modality-specific distinctiveness through an anchor-guided contrastive objective. To further account for modality imbalance and noisy correspondences, we model cross-modal interactions using unbalanced optimal transport. We evaluate the proposed approach on multiple TCGA cancer cohorts with paired histopathology and genomic data. TTA consistently improves survival prediction over recent multimodal survival models. Moreover, the learned prototype structures reveal interpretable cross-modal patterns associated with clinical outcomes.

Wenjing Liu, Qin Ren, Wen Zhang +2

Stony Brook University, Stony Brook, NY, USA · Johns Hopkins University, Baltimore, MD, USA · Brookhaven National Laboratory, Upton, NY, USA

Cancer Survival PredictionSurvival AnalysisCross-Modal AlignmentOncologyMultimodal Survival AnalysisMultimodal Contrastive Learning
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