Individual patient data (IPD) from clinical trials is the substrate for survival modeling, meta-analysis, and safety research, yet IPD is rarely released. Prior work has addressed only half of this gap: reconstructing Kaplan-Meier (KM) curves from published plots -- typically requiring manual digitization or human-in-the-loop correction -- while offering no mechanism for generating the adverse-event (AE) streams that constitute the other half of a patient record. We introduce KMGen, the first end-to-end framework that (i) fully automates KM curve extraction at accuracy competitive with human-guided tools, and (ii) generates synthetic per-patient AE trajectories from public trial registry records. The extraction stage is a fully automated agentic pipeline -- an agent generates code to extract each step in the KM curve -- achieving a mean Integrated Absolute Error (IAE) of 0.0151 on a 32-plot benchmark spanning clean, edge-case, and adversarial conditions. The IPD generation stage decouples patient archetype extraction from statistical sampling: an LLM distills the trial record into arm-specific statistics, adverse events, patient demographics, and risk multipliers. A mechanistic sampler generates patient events via clinical archetypes, bootstrap rank-correlation coupling to the empirical KM curve (preserving the marginal survival distribution exactly), and cycle-based AE scheduling with an induction/maintenance split. Across three held-out oncology trials spanning an order of magnitude in cohort size and 30 independent regenerations per trial, KMGen achieves mean integrated KM absolute difference $Δ_{\text{KM}}\,{\leq}\,0.051$, sex/ECOG JSD ${\leq}\,0.013$ on 5 of 6 demographic slots, and recovers ${\geq}\,71\%$ of the top-15 AEs by exact MedDRA term under a single fixed parameter set. The pipeline is released as open source at https://github.com/chufangao/kmgen.
Hemant Ishwaran, Eileen M. Hsich, Udaya B. Kogalur +1stat.ML cs.LG stat.ME
Clinical data sources such as electronic health records and wearable sensors record patient status repeatedly over follow-up, often at irregular times and on different schedules for different measurements. These data create opportunities for continuously updated, individualized risk prediction. Existing approaches, however, often simplify the temporal structure before modeling it. We introduce Random Hazard Forests (RHF), a survival tree ensemble that learns how a patient's hazard changes in continuous time as new measurements become available. RHF formulates the estimation problem directly through a nonparametric hazard likelihood for predictable covariate processes. An efficient working model guides tree construction, after which flexible time-varying hazards are estimated for each terminal node. Given any predictable covariate path, each tree follows the path through its terminal nodes over time and assembles the corresponding node-level hazards into a trajectory. Averaging these trajectories across trees yields the RHF pathwise hazard estimate. Because routing at each time uses only the covariate state available immediately beforehand, RHF accommodates internal longitudinal covariates without lookahead. Simulations and an intensive care application show that RHF accurately estimates changing risk under irregular and asynchronous covariate updates.
In survival analysis the way covariates act on the risk of an event often differs between early and late failure times, yet hazard- and mean-based summaries collapse this variation into a single number. Quantile-based modeling instead describes the full conditional distribution on the original time scale, but existing censored-data methods are either inflexible or produce logically inconsistent crossing quantile curves. We propose a Censored Non-crossing Quantile (CNQ) framework for right-censored data that jointly estimates several conditional survival quantiles and guarantees valid ordering by construction, with flexibility supplied by Kolmogorov-Arnold and Transformer backbones, and we establish a finite-sample excess-risk bound holding jointly across all fitted quantile levels. Across 27 simulation settings and six cohorts the framework attains lower pinball loss than quantile-, hazard- and tree-based competitors whenever the conditional distribution is asymmetric, with interval coverage closer to nominal on all six. In two clinical case studies (METABRIC, breast cancer; FLCHAIN, population mortality) it recovers covariate effects that vary across the survival distribution and would be hidden by a single hazard ratio, and yields coherent individualized quantile milestones. Code: https://github.com/BIG-S2/deepcnq
Paul Minchella, Stéphane Chrétien, Guillaume Metzler +2cs.LG
Machine learning has become an essential component of modern healthcare, where the integration of heterogeneous data sources offers unprecedented opportunities to improve clinical decision-making. Electronic Health Records (EHR) contain complementary information -- including narrative clinical reports, numerical measurements, and structured variables -- yet most survival models remain limited to a single modality or fail to exploit the temporal nature of patient trajectories. We propose MultiSigBERT, a unified framework for multimodal sequential survival modeling in oncology based on path signature representations. Here, narrative medical reports (free-text) are converted into sentence embeddings by extracting and averaging contextual word embeddings. These representations are then compressed via modality-specific PCA and concatenated with structured covariates to form joint temporal trajectories which are then encoded using the Signature transform, a tool from Rough Paths theory that efficiently captures higher-order temporal interactions across modalities without supervision needed. The computed Signature features are finally incorporated as high dimensional features into a LASSO-regularized Cox model to estimate individualized risk scores. The performance of our novel MultiSigBERT pipeline is illustrated on the analysis of a real-world oncology cohort from the Léon Bérard Center, comprising over 120,000 medical reports and structured records from more than 2,500 patients. The model achieves a concordance index of 0.743 (sd 0.029) on an independent test set, demonstrating the benefit of jointly modeling multimodal temporal dynamics together with patient-level geometric structure for survival prediction.
Recovering geographic variation in survival requires separating spatial risk from patients' clinical characteristics, a problem complicated by prognostic covariates that are themselves spatially structured. We develop a nonparametric two-stage method for this separation. A clinical survival tree fit to the covariates alone supplies leaf Nelson-Aalen cumulative hazard residuals, transferring the censored survival structure to a clinically adjusted scale without imposing a functional form on the clinical hazard, and a second tree fit to these residuals on the coordinates recovers the spatial structure. Both stages are kernel dipole-splitting survival trees, so the resulting spatial risk map is piecewise constant, with sharp, possibly curved boundaries. We establish when the residuals recover the spatial signal: under a multiplicative frailty and an exogeneity condition, they are free of the clinical covariates given location and stochastically ordered by the frailty. An expansion of the frailty Laplace exponent quantifies their approximate exponentiality and identifies the leading remainder. These results assume consistency of the first stage rather than a model class, so the construction extends to other survival estimators. On the LeukSurv leukemia data the method agrees with a Bayesian Gaussian random field frailty about where risk is elevated while resolving sharp adjacencies the smooth surface averages away, and an unadjusted spatial analysis misattributes clinical variation to location. Simulations with known zones, including a sweep through graded violations of exogeneity, locate the point at which the two contributions cease to be separately identifiable, with the smooth benchmark degrading in parallel as that point is approached.
Zhiyuan Yang, Jiahao Cheng, Vincent Quoc-Huy Trinh +1cs.CV
Transformer models are increasingly used for whole-slide image analysis in computational pathology. Yet, WSIs differ fundamentally from natural images: neighbouring patches often contain highly similar tissue type, stain, texture, and cellular composition. We identify this local spatial redundancy as a pathology-specific failure mode of self-attention, where dominant neighbourhood features can be repeatedly mixed into patch-tokens and weaken subtle diagnostic or prognostic deviations. We propose Gated Spatial Redundancy Projection (Gated SRP), a lightweight drop-in correction module for self-attention layers. For each patch token and attention head, Gated SRP estimates a local redundancy axis from neighbouring value vectors, projects the attention output onto this axis, and applies a learned signed gate to correct the redundancy-aligned component geometrically. Across five TCGA survival cohorts, Gated SRP obtains the highest mean C-index among the compared attention variants in all cohorts, with an average improvement over the base attention, while adding only +0.02% parameters. Across five slide-level classification datasets, it improves the base attention on 12 of 16 reported metrics and achieves the best AUC on three datasets. Code is publicly available at https://github.com/AtlasAnalyticsLab/GatedSRP.
Lev V. Utkin, Stanislav K. Kogan, Andrei V. Konstantinovcs.LG stat.ML
This work presents a novel attention-based framework for estimating the Individual Probability of Treatment Benefit (IPTB) in survival analysis contexts. The proposed model, called Surv-IPTB, directly quantifies the probability that a specific patient will experience extended survival time under treatment versus control. We reformulate IPTB estimation as a binary classification problem, leveraging pairwise patient comparisons across treatment and control cohorts. The framework incorporates a principled handling of right-censored observations through imprecise probability representations, where uncertain treatment effects are characterized by interval-valued probabilities. An attention mechanism with learnable query-key transformations enables flexible, data-driven aggregation of pairwise comparisons, while simultaneously learning soft class probabilities for censored cases. Through extensive experiments on synthetic datasets with complex nonlinear structures, including spiral, bell-shaped, and circular feature spaces, we demonstrate that our approach maintains robust performance across varying censoring rates and treatment effect strengths. The model consistently outperforms meta-learner baselines (T-learner and S-learner) equipped with random survival forests, Cox proportional hazards, and Beran estimators, particularly in challenging nonlinear scenarios where conventional methods exhibit significant degradation. The results establish the proposed attention-based framework as a scalable and statistically principled solution for personalized treatment benefit assessment in survival settings. The code implementing the model is publicly available.
Digital pathology relies on high-resolution whole slide images for accurate diagnosis, yet limitations in imaging devices, storage, and transmission often make lower-resolution pathology images more common in clinical workflows. Current super-resolution techniques often tend to smooth diagnostically relevant morphology, leading to over-smoothed textures and semantic drift that compromise downstream clinical interpretation. To this end, we develop the Structural Semantic Synergy Diffusion Model (S3-Diff), a diffusion framework for high-fidelity super-resolution of pathological images. The core of S3-Diff is Specimen-aware Structural Anchoring (SSA), which combines prognosis-aware tissue support extracted by a fixed SAM with LR-HR gradient discrepancies to generate a specimen-specific structural anchor to preserve pathological morphology. Concurrently, we introduce Structure-guided Semantic Fidelity Tuning (SSFT) to adapt DINOv3 representations using SSA-derived structural supervision. SSFT combines the adapted semantic energy with LR-derived edge and grayscale cues. The resulting control guides denoising to suppress stochastic artifacts and maintain structural consistency. Extensive experimental results demonstrate that S3-Diff consistently outperforms state-of-the-art methods in both reconstruction quality and downstream survival analysis performance. The source code will be made public.
Shashank Yadav, David M. Routman, Andrew Y. K. Foongq-bio.QM cs.LG
Survival analysis is an established framework for analyzing time-to-event data, yet many clinical machine learning studies still binarize the outcome before model training. This practice excludes censored patients, collapses temporal information into a single threshold, and can affect which features are selected as prognostically relevant. We examine the cost of this binarization in the context of Bayesian network (BN) feature selection, using two recent publications as case studies: one that applies BN-based feature selection to a head-and-neck cancer cohort and a second surgical cohort study that, while not BN-based, likewise binarizes its survival endpoint. We replace the binary scoring function with the Cox partial log-likelihood for feature-to-outcome edges, a modification we call the Survival-Aware Bayesian network, and recover prognostic features that binarization misses. Our ablation experiment confirms that the improvement is driven by the time-to-event scoring formulation rather than by retaining more patients. The results generalize across five endpoint-cohort combinations in head-and-neck cancer and extend to three further cancer types (breast, colorectal, and kidney). We propose that clinical studies with survival outcomes should use time-to-event methods by default, as binarization discards the prognostic signal retained by survival analysis.
Begoña B. Sierra, Colin McLean, Peter S. Hall +2stat.ML cs.LG
A wide range of statistical and machine learning methods have been proposed for survival analysis with competing risks, where the occurrence of one event (i.e., cancer death) precludes the occurrence of other events (i.e., cardiovascular disease death). Despite these methodological advances, their systematic evaluation and adoption are limited by the lack of comprehensive, reproducible and extensible benchmarking frameworks. We developed an open-source benchmarking framework for competing risks models that enables their systematic comparison across multiple datasets under different aspects of performance; calibration, discrimination, overall prediction error and clinical utility. We additionally introduce an extension of SHAP for competing risks, allowing model-agnostic interpretability of covariates contributions over time. All our code is publicly available via GitHub:https://github.com/BBolosSierra/CompRisksBenchmark
Tijn Jacobs, Stéphanie L. van der Pas, Wessel N. van Wieringenstat.ME stat.ML
We develop the Bayesian fusion forest, a nonparametric framework to estimate heterogeneous treatment effects on survival outcomes by combining a randomised controlled trial and real-world data. The framework relaxes the unconfoundedness assumption on the real-world data by assuming instead that the treatment effect transports across the two sources. Our method opens up right- and interval-censored outcomes to data fusion. We model the survival time with an accelerated failure time decomposition into a shared baseline prognosis, a source-specific deviation, a treatment effect, and a confounding function. The confounding function absorbs the confounding bias in the real-world data. Each component receives a Bayesian tree ensemble prior. The shared baseline prognosis borrows strength across sources, while the deviation captures between-source heterogeneity. A hierarchical Dirichlet process mixture models the error distribution nonparametrically. A simulation study shows efficiency gains over a trial-only analysis across varying levels of confounding and between-source heterogeneity. We combine the ACTG 175 trial with the Multicenter AIDS Cohort Study to estimate the effect of combination antiretroviral therapy for HIV. The fusion identifies a benefit for nearly every patient whereas the trial alone is inconclusive.
Kai Wang, Meixu Chen, Elie Nasr +2cs.CV physics.med-ph
We present HERMES (Hybrid Ensemble for Radiotherapy-target segmentation, Malignancy staging, and Event-free Survival), a single containerized algorithm for the three HECKTOR 2026 subtasks: segmentation of the primary tumor (GTVp) and pathological lymph nodes (GTVn), radiological T/N staging, and recurrence-free survival (RFS), computed from a paired FDG-PET/CT scan and an electronic health record. A 10-fold ensemble of STU-Net Small networks produces the segmentation; the predicted mask then drives two downstream tasks. Rather than pass a generic radiomics vector to the staging models, we derive from the predicted masks a compact set of geometry features aligned with the size and number axes of AJCC/UICC 7th-edition radiological N/T staging. On internal cross-validation these features raise N-stage balanced accuracy from 0.691 to 0.720 (+0.030), our largest single design gain, at lower feature dimensionality. For prognosis we combine complementary deep and clinical risk experts in an equal-weight ensemble, and train one deep expert with a concordance-tracking survival loss of our own, whose value approximates the concordance index during training. Every component was selected on honest out-of-fold predictions under a regularization-oriented protocol, with no tuning on the public validation set, and deployed as two decorrelated submissions. On the HECKTOR 2026 validation leaderboard, HERMES achieved a weighted score of 0.6454 (Mean Dice 0.641, T balanced accuracy 0.580, N balanced accuracy 0.642, RFS C-index 0.679) and qualified for the testing phase. Team: AMC_HNC.
Large-scale observational studies increasingly rely on AI pipelines to extract structured variables from unstructured clinical records. A common workflow separates the data vendor, who validates extraction accuracy with a gold-standard sample, from the downstream researcher, who receives only the extracted dataset and summary accuracy statistics. We develop a bias-correction framework for the Cox proportional hazards model when covariates are subject to AI extraction error. Within a unified multivariate calibration framework, we show that the naive Cox estimator's bias decomposes into a leading-order calibration term and a second-order residual that vanishes as extraction accuracy improves. The leading-order term yields a corrected estimator that operates as a post-hoc matrix multiplication on the output of any standard Cox software. We further derive bias-adjusted confidence intervals that incorporate calibration uncertainty and a sensitivity diagnostic for assessing whether the neglected residual could materially affect inference. Synthetic data experiments with cross-dependent extraction errors and controlled nonlinear calibration violations confirm that the correction substantially reduces bias and achieves near-nominal coverage even under mild violations of the linear calibration assumption. The framework yields a concrete reporting specification: a short list of summary statistics that data vendors should provide alongside any AI-extracted covariate dataset used in survival analysis.
In this work, we propose K-SurvMeans, a novel extension of K-Means for clustering survival data. The method explicitly uses the survival outcome in the clustering process to optimize cluster centers, thereby maximizing pairwise survival differences between clusters. The objective function encourages the clusters to be well-separated from the survival perspective. Since the resulting optimization problem is non-differentiable, we employ the Particle Swarm algorithm for the Optimization process. To further improve flexibility and mitigate the curse of dimensionality, we extend the framework to operate in a learned low-dimensional latent space obtained via a dimensionality reduction. This allows the method to capture better-separated clusters and enhance optimization efficiency by reducing the search space. Experiments on multiple publicly available benchmark survival datasets demonstrate that K-SurvMeans consistently yields clusters with improved separation in survival distributions compared to existing deep learning-based survival clustering methods.
Accurate fracture risk prediction is important for osteoporosis management, but commonly used clinical tools may not fully use information available in electronic health records (EHRs) and dual-energy X-ray absorptiometry (DXA) reports. We developed and externally validated time-to-event fracture prediction models among adults aged 50 years or older with clinically obtained DXA reports in 2 US health care systems. The development cohort was derived from NewYork-Presbyterian/Weill Cornell Medical Center and the external validation cohort from the Indiana Network for Patient Care. Predictors included demographics, lifestyle factors, prior fracture, comorbidities, medication exposures, osteoporosis treatment history, and DXA-derived T-scores extracted from radiology reports. The outcome was time from index DXA to first incident fragility fracture identified from structured diagnosis codes. We evaluated penalized Cox regression, random survival forest, gradient-boosting survival, and XGBoost survival models using 2 prespecified predictor settings and compared discrimination with clinically reported FRAX major osteoporotic fracture probabilities. The development cohort included 11,510 adults, of whom 858 sustained incident fragility fractures; the external validation cohort included 1,932 adults, of whom 180 sustained fractures. In internal validation, the expanded Cox model achieved a mean Harrell C-index of 0.779, compared with 0.653 for FRAX. In external validation, the corresponding Cox model achieved a Harrell C-index of 0.714, compared with 0.590 for FRAX; gradient-boosting survival had the highest external discrimination (0.725). EHR- and DXA-enhanced models showed better discrimination than clinically reported FRAX scores in this DXA-tested population, but calibration assessment, prospective evaluation, and implementation workflow assessment are needed before clinical use.
Whole-slide survival models commonly provide risk rankings without calibrated statements about individual event times. We evaluate fixed-cutoff drcosarc, a post-hoc conformal wrapper for discrete-time multiple-instance learning survival heads using frozen UNI2-h representations, in an internal 18-configuration sweep across five TCGA cohorts and an external five-configuration evaluation across three CPTAC cohorts. We distinguish configuration--fold--split summaries of the inverse-probability-of-censoring-weighted (IPCW) estimate and median lower predictive bound (LPB) from a hierarchy-aware patient-ensemble estimand of the mean drcosarc--naive LPB difference. At $α=0.1$, the drcosarc IPCW estimate was nearest 0.90 in KIRC, LUAD, and STAD. Patient-ensemble drcosarc--naive intervals excluded zero in KIRC, KIRP, STAD, UCEC, and CPTAC-CCRCC, but included zero in internal LUAD, CPTAC-LUAD, CPTAC-UCEC, and the internal LUSC extension. In a 20-replicate low-censoring semi-synthetic setting with known event times, drcosarc empirical coverage was 0.9129 [0.9053, 0.9207]. An exploratory analysis supported a head-error-by-censoring interaction within that data-generating process. In a two-cohort ABMIL sensitivity analysis, increasing the hazard grid to $K=16$ raised localized marginal IPCW estimates above the prespecified 0.87 threshold and yielded positive paired LPB differences, although worst-group estimates remained below 0.87. Overall, performance was cohort dependent, and its interpretation changed with the patient-level unit, estimand, and censoring assumptions.
Recent work has argued normatively, on synthetic data, that evaluating survival models by discrimination alone (concordance index) yields systematically misleading model comparisons, because the metric ignores calibration and time-dependent accuracy. Whether this matters for real, published, non-clinical models has not been tested. We reproduce three published survival-ML models across three structurally distinct domains -- hard-drive failure prediction, peer-to-peer credit default, and user disengagement on digital platforms -- validate our instrument against the anchor paper's own synthetic experiment, and test five pre-registered hypotheses under a Holm-corrected family-wise error rate. Three of five reject (though one pre-registered threshold clears by a narrow margin). A model reproducing the published literature's discrimination almost exactly (C = 0.9595 vs. 0.958 reported) fails a formal calibration test at p < 0.001; a broad feature-ablation search finds no single attribute responsible for its discrimination, so the calibration failure is not a trivial shortcut artifact. A lender's estimated default risk is biased upward by roughly two percentage points, growing to nearly four in the riskiest segment, when loan prepayment is treated as non-informative censoring rather than a competing risk. A platform's churn model shows probability estimates that degrade with the horizon even as global discrimination stays within the pre-registered C-index band. A direct test of whether metric choice inverts model preference does not reject, though with limited power given two to three models per domain; the failure mode we document is better characterized as misplaced confidence in a chosen model than as choosing the wrong one. We release a pre-registered evaluation harness with full code and an annotated notebook, so these results can be verified independently and the audit extended.
Background. Predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is central to trial enrichment and care planning, yet existing models provide no individual-level uncertainty estimates and rarely include transparent leakage audits. We introduce the first application of persistent homology to longitudinal clinical trajectory point clouds for this task, and the first split-conformal individual risk guarantee for any AD-conversion model. Methods. We analysed 741 MCI subjects (240 converters, 32.4%) from ADNI with a uniform 4-year follow-up cap. Five leakage sources were corrected; without them a naive pipeline achieved AUC=0.934, inflated by +0.075. Vietoris-Rips persistent homology and sublevel-set proxies were combined with trajectory slopes and engineered features (76 total) in a stacking ensemble evaluated by 5-fold cross-validation. Results. Cox and Random Survival Forest models with TDA features achieved concordance C=0.799 and C=0.826 versus C=0.753 and C=0.812 without (+0.045 and +0.014). The primary nested AUC is 0.840 (same-fold bound 0.866); external AUC was 0.879 on a zero-overlap ADNI-2/GO/3 cohort. H0 persistence entropy was the top SHAP feature and significantly associated with APOE4 dosage (Spearman r=-0.191, p<0.0001, Bonferroni-corrected). Cross-conformal coverage was 90.4%+-2.2% (target 90%); empirical external coverage 96.9%. Maximum fairness gap in false-negative rate across seven subgroups was 0.092. Conclusions. We propose H0 persistence entropy as a topological biomarker of cognitive decline and demonstrate that a leakage-audited, conformally calibrated pipeline reaches competitive accuracy with individual-level uncertainty quantification not previously available for this task.
Xiaodi Li, Munhuwan Lee, Pengyang Li +5stat.AP cs.AI cs.LG
Traditional randomized trials often obscure clinically meaningful heterogeneity in treatment response by focusing on average effects. Leveraging real-world data to emulate clinical trials and estimate heterogeneous treatment effects (HTEs) offers a promising path toward more precise and efficient trial design. In this study, we emulate the DAPA-HF trial using electronic health records from the Mayo Clinic Cloud (MCC) to investigate whether HTE-guided stratification can identify patient subgroups with distinct treatment responses to dapagliflozin versus placebo in patients with heart failure with reduced ejection fraction. All-cause mortality was evaluated using Cox proportional hazards models, with HTEs estimated using a Meta-S learner and subgroups defined using a decision tree-based thresholding approach. In the overall cohort of the emulation, no significant treatment difference was observed (HR, 1.681; 95% CI, 0.828-3.413; p = 0.1507). However, compared with the overall emulated cohort, in which dapagliflozin showed no statistically significant survival benefit, HTE-driven stratification identified subgroups with significant and directionally distinct treatment effects. The beneficial (low-HTE) subgroup showed a significant survival benefit from dapagliflozin (HR = 0.203, 95% CI, 0.087-0.476, p = 0.0002), whereas the harmful (high-HTE) subgroup showed a significant harmful association with markedly increased mortality risk (HR = 6.680, 95% CI, 2.759-16.171, p < 0.0001). These findings indicate that HTE-guided stratification can uncover clinically meaningful beneficial and harmful treatment-effect patterns that are masked in the full-cohort emulation.
Meixu Chen, Kai Wang, Jing Wangcs.LG cs.CV stat.ML
Deep survival models are evaluated almost exclusively by the concordance index (C-index), yet they are commonly trained using likelihood objectives such as the Cox partial likelihood, discrete-time negative log-likelihood, and DeepHit likelihood. This mismatch is usually considered acceptable because the C-index can be recomputed on validation data during training. However, for end-to-end training of high-capacity encoders on small, heavily censored oncology cohorts, frequent C-index evaluation is computationally expensive, making the loss value itself an important signal for monitoring, early stopping, and model selection. We show that likelihood losses are unreliable for this purpose and propose a value-monotone concordance loss. We prove that every strictly proper survival likelihood admits directions where the loss decreases while the C-index remains unchanged, causing the loss value to decouple from ranking performance. We then study a sigmoid concordance loss (SCL), whose value approximates one minus the C-index up to a temperature term, ensuring that lower loss corresponds to higher C-index during optimization. The loss is architecture agnostic and reduces to a convex survival ranking support vector machine for linear models. Across eighteen datasets from four modalities using a unified five-fold cross-validation protocol, SCL achieves discrimination comparable to standard likelihood losses and is the best or within one standard deviation of the best C-index. Unlike likelihood losses, SCL maintains a strong correlation between loss value and C-index during training, with rank correlations of 0.96 to 0.99 compared with -0.03 to 0.53 for likelihood losses. Calibration measured by the integrated Brier score is comparable. SCL provides a value-monotone optimization objective whose value can serve as a reliable surrogate for the C-index during expensive end-to-end training.
Zongliang Yue, Qi Li, Terry Heiman-Patterson +3cs.LG cs.IR stat.ML
Amyotrophic lateral sclerosis (ALS) is a progressive and heterogeneous neurodegenerative disease in which predicting clinically meaningful milestones, such as assistive device use, remains challenging. We developed a time-to-event, digital-twin-inspired framework that integrates longitudinal ALS Functional Rating Scale-Revised (ALSFRS-R) trajectories with survival modeling to support individualized prediction of functional decline and assistive device utilization. We constructed a harmonized longitudinal dataset by integrating diagnosis records, ALSFRS-R assessments, activities of daily living, and demographic information, followed by preprocessing to ensure data quality, temporal alignment, and cohort consistency. Correlation-based clustering identified coherent functional domains spanning bulbar, upper limb, axial, lower limb, and respiratory systems. Generalized additive mixed models characterized nonlinear, domain-specific functional decline across all domains. In addition, a temporal machine learning model was developed to predict longitudinal functional decline and capture stage-dependent disease progression. Cox proportional hazards modeling further identified lower limb function, particularly walking and stair climbing, as the strongest predictors of earlier wheelchair access. Building on these results, we implemented a digital twin-inspired temporal machine learning-based time-to-event (TTE) model that generates individualized survival curves and dynamically predicts wheelchair-free survival. This framework provides a scalable, interpretable, and clinically actionable approach for linking ALS progression with personalized decision support, with applications in proactive care planning, clinical trial stratification, and precision medicine.
Yanqi Xu, Hui Dai, Carlos Fernandez-Granda +2cs.LG stat.AP
Survival models can model time-to-event outcomes using partially observed data. They are widely used in clinical prediction, including cancer risk, disease progression, treatment response, and mortality. Recent models often rely on rich inputs collected at a specific clinical encounter, such as medical images, laboratory tests, electronic health record snapshots, or sensor measurements. In large retrospective datasets, these inputs are usually collected over many calendar years. As a result, they may contain clues about when they were acquired through changes in devices, protocols, documentation, patient mix, or clinical practice. This creates a potential failure mode when outcomes are observed only up to a fixed study end date. More recent records necessarily have less potential follow-up than older records. A model that can infer the record date from the input may therefore learn to predict how much follow-up was available rather than the patient's true risk of experiencing the event. We call this failure mode administrative-cutoff leakage. In this paper, we characterize when this leakage can occur, distinguish it from classical informative censoring and genuine temporal changes in risk, and propose practical ways to detect it. In simulations, we show that administrative-cutoff leakage can inflate fixed-horizon AUC and can also affect Harrell's C-index under realistic follow-up patterns. We then demonstrate the same behavior in a real mammography cohort. These results motivate a simple design principle for survival prediction: for an n-year prediction task, the dataset should provide at least n years of potential follow-up after the latest input date. Otherwise, the models may be subject to bias induced by administrative-cutoff leakage.
Yue Lyu, Steven H. Lin, Xuelin Huang +1stat.ME stat.ML
Time-to-event prediction from tabular patient data is central to prognosis and biomedical decision support, but right-censored follow-up prevents direct use of ordinary regression labels. Tabular foundation models offer reusable prediction machinery for modest heterogeneous datasets, yet they generally assume fully observed outcomes. We introduce SurvFM-RMST, a censoring-aware target-interface framework that converts survival outcomes into jackknife pseudo-observation targets for restricted mean survival time, enabling multiple tabular backbones to perform horizon-specific RMST regression without survival-specific fine-tuning. In controlled simulations with known conditional RMST, SurvFM-RMST recovered restricted event-free time accurately, and pseudo-RMST targets outperformed naive restricted observed-time and event-only targets. Across 36 eligible static SurvSet datasets, SurvFM backbones were competitive with established survival and RMST-regression comparators, though relative performance varied by endpoint, horizon and practical constraints. Predicted RMST further stratified held-out patients into groups with ordered observed event-free time and event enrichment. Overall, the results support pseudo-RMST target construction as a portable interface between censored survival data and tabular foundation-model prediction.
Medical time-to-event data are frequently subject to competing risks, where the occurrence of one terminal event precludes the others and standard survival methods that treat competing events as censoring yield biased absolute-risk estimates. Valid analysis instead targets the cause-specific cumulative incidence function (CIF). This methodology has been available to applied researchers almost exclusively through R packages, forcing Python-based machine-learning workflows into a Python-to-R round trip. We present comprisk, a scikit-learn-compatible Python toolkit that puts the canonical competing-risks methods behind one API: a scalable competing-risks random survival forest, Fine-Gray subdistribution-hazard regression and a penalized variant, cause-specific Cox regression, the Aalen-Johansen CIF estimator, and Gray's K-sample test, together with competing-risks-aware model evaluation. Every estimator is validated numerically against its R reference implementation. The forest uses a histogram-based, numba-compiled split kernel that fits 10-22x faster than randomForestSRC at comparable discrimination on real clinical cohorts and scales to n = 10^6 on a consumer CPU. comprisk is distributed on PyPI and lets applied researchers run correct, scalable competing-risks analysis without leaving the Python scientific stack.
Survival analysis on Whole Slide Images (WSIs) is important in computational pathology for prognosis estimation and treatment planning. However, existing survival models are typically trained independently for each cancer cohort, making continual adaptation computationally expensive for gigapixel-scale WSIs. In this study, we propose MergeSurv, a merging-based continual learning framework for WSI survival analysis. A pathology vision-language foundation model is independently fine-tuned on each task, and the learned parameters are sequentially merged into a unified model without storing previous training data. We further investigate two inference strategies: One-for-All (OFA) and Voting-Expert Aggregation (VEA). Experiments on four TCGA cohorts demonstrate that MergeSurv outperforms naive fine-tuning as well as representative regularization-based and rehearsal-based continual learning methods, while effectively reducing catastrophic forgetting. The results suggest that model merging is a promising direction for scalable and privacy-preserving continual learning in computational pathology.
Niccolò Maria Rizzi, Eugenio Lomurno, Alberto Archetti +1cs.LG
Survival analysis models time-to-event data, but in clinical settings training data are costly and scarce: events accrue over years of follow-up, cohorts are small, and privacy regulations restrict sharing across institutions. Tabular generative models promise augmentation and privacy-preserving cohort sharing, yet are themselves data-hungry -- on the small cohorts typical of survival analysis, a single generator rarely characterizes the population well enough for downstream models trained on its output to match real-data performance. FoGS (Filtered Mixture-of-Generators for Survival analysis) reframes synthetic-data construction as sample selection rather than generation. A candidate pool is drawn from four architecturally distinct tabular generators, and each sample is scored by an ensemble of seven survival models trained on real data, using proper scoring rules as a per-sample plausibility proxy. A two-level pipeline optimizes, in its outer loop, a selection policy -- generator quotas, scorer weights, a random complement, and stratified balancing on event time and censoring -- against held-out downstream performance, while an inner loop tunes the downstream model (XGBoost-Cox). On 16 public datasets under train-on-synthetic, test-on-real (C-index and IBS, $0$--$100$ scale), FoGS yields mean improvements of $+2.17$ in C-index and $+0.67$ in IBS, improving both metrics on 9 of 16 datasets and at least one on 13 (one-sided Wilcoxon $p=0.039$ and $p=0.035$). It matches or exceeds real-data training on most cohorts, with no significant change in nearest-neighbour privacy margin relative to unfiltered sampling. Sample filtering over a heterogeneous generator pool is thus a viable substitute for real-data training in privacy-restricted clinical settings.
Parkinson's disease (PD) selectively impairs distinct stages of motor control. Using backspace events as natural error-correction episodes in the public neuroQWERTY MIT-CSXPD dataset (n=57 subjects, 27 PD with UPDRS-III scores), we test whether passively-collected keystroke timing dissociates a variability-based pre-error monitoring signal from a speed-based post-error recovery signal. Pre-error typing instability does not track PD severity (r=-0.072, p=0.721), while post-error pause duration does (r=+0.656, p=0.0002; subject-level OLS p=1.2x10^-4, n=27, primary analysis given within-subject event clustering). A mixed-effects log-normal model with a random subject intercept confirms this while retaining full event-level power (coef=0.0250, p=1.2x10^-4, n=1,563 events), closely matching the subject-level OLS despite an unrelated estimation strategy. Error-detection latency also correlates with UPDRS-III (r=+0.660), confirming the dissociation is between variability and speed, not detection and correction per se. A log-normal accelerated failure time model yields a coefficient of 0.0255 (bootstrap 95% CI [0.0146, 0.0357]), a 2.6% increase per UPDRS-III point. After controlling the immediately thecoefficient attenuates to 0.0133 (p=3.1x10^-21),consistent w timingincrement above general bradykinesia. Results reacross both S2:r=+0.645), survive jackknife exclusion of every subject, andnatingfinger-tapping and mPower smartphone tapping (group AUC=0.836). cellent(ICC(2,1)=0.945, n=20).
Abigail Loe, Susan Murry, Zhenke Wustat.ML cs.LG stat.AP
Alternating recurrent events -- event-times of a specific nature that trigger a secondary refractory period -- occur in a wide-range of fields, including behavioral science, criminal justice, and biostatistics. Analysis of these events requires careful attention to the statistical nuance, including correlated observations and repeated outcomes subject to potential censoring. We develop an online dynamic prediction framework appropriate for predicting subsequent alternating recurrent events, by developing neural network theory for a statistical audiences and applying inverse probability weighted pseudo-observations. The proposed model is applied to dynamically predict alternating recurrent event-free time, showing good performance in simulation, and outstanding capability in application to predicting periods of low mood for first-year medical residents. We close with a discussion.
Multimodal survival analysis utilizing whole slide images (WSIs) and genomic profiles is fundamental for cancer prognosis. Recently, state-space models like Mamba have emerged as powerful tools for sequence modeling. However, translating this success to complex multimodal tasks is hindered by two critical limitations. First, conventional fusion strategies assume a static multimodal interaction strength, ignoring the fluctuating diagnostic importance of each modality across different patients and local regions. Second, the standard Mamba architecture processes tokens along predefined physical paths. This rigid scanning disrupts the semantic continuity of spatially scattered medical features and exacerbates long-range decay. To address these challenges, we introduce AdaSurvMamba as a novel adaptive framework for multimodal survival analysis. The framework features a Dual-Scale Importance-Aware Reconstruction (DSIR) module to dynamically modulate cross-modal interaction strength. It evaluates diagnostic importance at both the sequence and token levels to reconstruct the input representations. Furthermore, we propose a Semantic Aggregation Scanning (SAS) module to overcome contextual fragmentation. The SAS module dynamically reorganizes discrete tokens into semantically continuous sequences via a shared prototype pool. It explicitly modulates the state transition step size using global modality context and semantic priors to adaptively control the information absorption rate. Experiments across five TCGA cohorts demonstrate consistent gains over existing methods. Code is available at https://github.com/zjlGO/AdaSurvMamba.
Natalia Moreno-Blasco, Anusha Ihalapathirana, Pekka Siirtola +1cs.LG q-bio.QM stat.ME stat.ML
Survival analysis is central to clinical decision-making, yet reliable time-to-event models require large, diverse cohorts that are rarely available at a single institution, while privacy regulations restrict the centralization of patient data. Federated learning (FL) offers a privacy-preserving alternative by training shared models without exchanging raw data, but its effectiveness for survival modeling under realistic, heterogeneous conditions remains insufficiently understood. This paper presents a systematic, multi-model evaluation of federated survival analysis on a cross-institutional breast cancer cohort with naturally heterogeneous distributed clients. Three representative survival models, the Cox Proportional Hazards model, DeepSurv, and Random Survival Forest (RSF), are compared across centralized, local, and federated training, and three federated optimization strategies (FedAvg, FedProx, and FedAdam) are assessed for the gradient-based models. Results show that FL consistently outperforms local training and approaches, and occasionally exceeds, centralized performance, while RSF offers the best overall balance of discrimination, calibration, and robustness across heterogeneous clients. We further find that performance depends on the diversity of client distributions, and that FedAvg and FedProx are stronger and more stable than FedAdam. Based on these findings, we derive practical, decision-oriented guidelines mapping data, privacy, interpretability, and resource constraints to recommended model and training-paradigm choices for federated survival modeling in healthcare.