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Efficient and scalable clustering of survival curves

Villanueva, Nora M., Sestelo, Marta, Meira-Machado, Luis

arXiv.org Machine Learning

Survival analysis encompasses a broad range of methods for analyzing time-to-event data, with one key objective being the comparison of survival curves across groups. Traditional approaches for identifying clusters of survival curves often rely on computationally intensive bootstrap techniques to approximate the null hypothesis distribution. While effective, these methods impose significant computational burdens. In this work, we propose a novel approach that leverages the k-means and log-rank test to efficiently identify and cluster survival curves. Our method eliminates the need for computationally expensive resampling, significantly reducing processing time while maintaining statistical reliability. By systematically evaluating survival curves and determining optimal clusters, the proposed method ensures a practical and scalable alternative for large-scale survival data analysis. Through simulation studies, we demonstrate that our approach achieves results comparable to existing bootstrap-based clustering methods while dramatically improving computational efficiency. These findings suggest that the log-rank-based clustering procedure offers a viable and time-efficient solution for researchers working with multiple survival curves in medical and epidemiological studies.


Methodology for Comparing Machine Learning Algorithms for Survival Analysis

Cardoso, Lucas Buk, Angelo, Simone Aldrey, Bonilha, Yasmin Pacheco Gil, Maia, Fernando, Ribeiro, Adeylson Guimarães, Curado, Maria Paula, Fernandes, Gisele Aparecida, Parro, Vanderlei Cunha, Cipparrone, Flávio Almeida de Magalhães, Filho, Alexandre Dias Porto Chiavegatto, Filho, Victor Wünsch, Toporcov, Tatiana Natasha

arXiv.org Artificial Intelligence

This study presents a comparative methodological analysis of six machine learning models for survival analysis (MLSA). Using data from nearly 45,000 colorectal cancer patients in the Hospital-Based Cancer Registries of São Paulo, we evaluated Random Survival Forest (RSF), Gradient Boosting for Survival Analysis (GBSA), Survival SVM (SSVM), XGBoost-Cox (XGB-Cox), XGBoost-AFT (XGB-AFT), and LightGBM (LGBM), capable of predicting survival considering censored data. Hyperparameter optimization was performed with different samplers, and model performance was assessed using the Concordance Index (C-Index), C-Index IPCW, time-dependent AUC, and Integrated Brier Score (IBS). Survival curves produced by the models were compared with predictions from classification algorithms, and predictor interpretation was conducted using SHAP and permutation importance. XGB-AFT achieved the best performance (C-Index = 0.7618; IPCW = 0.7532), followed by GBSA and RSF. The results highlight the potential and applicability of MLSA to improve survival prediction and support decision making.


Deep Multi-task Gaussian Processes for Survival Analysis with Competing Risks

Neural Information Processing Systems

Designing optimal treatment plans for patients with comorbidities requires accurate cause-specific mortality prognosis. Motivated by the recent availability of linked electronic health records, we develop a nonparametric Bayesian model for survival analysis with competing risks, which can be used for jointly assessing a patient's risk of multiple (competing) adverse outcomes. The model views a patient's survival times with respect to the competing risks as the outputs of a deep multi-task Gaussian process (DMGP), the inputs to which are the patients' covari-ates. Unlike parametric survival analysis methods based on Cox and Weibull models, our model uses DMGPs to capture complex non-linear interactions between the patients' covariates and cause-specific survival times, thereby learning flexible patient-specific and cause-specific survival curves, all in a data-driven fashion without explicit parametric assumptions on the hazard rates. We propose a varia-tional inference algorithm that is capable of learning the model parameters from time-to-event data while handling right censoring. Experiments on synthetic and real data show that our model outperforms the state-of-the-art survival models.


Learning a Distance for the Clustering of Patients with Amyotrophic Lateral Sclerosis

Tejedor, Guillaume, Peralta, Veronika, Labroche, Nicolas, Marcel, Patrick, Blasco, Hélène, Alarcan, Hugo

arXiv.org Artificial Intelligence

Amyotrophic lateral sclerosis (ALS) is a severe disease with a typical survival of 3-5 years after symptom onset. Current treatments offer only limited life extension, and the variability in patient responses highlights the need for personalized care. However, research is hindered by small, heterogeneous cohorts, sparse longitudinal data, and the lack of a clear definition for clinically meaningful patient clusters. Existing clustering methods remain limited in both scope and number. To address this, we propose a clustering approach that groups sequences using a disease progression declarative score. Our approach integrates medical expertise through multiple descriptive variables, investigating several distance measures combining such variables, both by reusing off-the-shelf distances and employing a weak-supervised learning method. We pair these distances with clustering methods and benchmark them against state-of-the-art techniques. The evaluation of our approach on a dataset of 353 ALS patients from the University Hospital of Tours, shows that our method outperforms state-of-the-art methods in survival analysis while achieving comparable silhouette scores. In addition, the learned distances enhance the relevance and interpretability of results for medical experts.


PISA: An AI Pipeline for Interpretable-by-design Survival Analysis Providing Multiple Complexity-Accuracy Trade-off Models

Schlender, Thalea, Romme, Catharina J. A., van der Linden, Yvette M., van Lonkhuijzen, Luc R. C. W., Bosman, Peter A. N., Alderliesten, Tanja

arXiv.org Artificial Intelligence

Survival analysis is central to clinical research, informing patient prognoses, guiding treatment decisions, and optimising resource allocation. Accurate time-to-event predictions not only improve quality of life but also reveal risk factors that shape clinical practice. For these models to be relevant in healthcare, interpretability is critical: predictions must be traceable to patient-specific characteristics, and risk factors should be identifiable to generate actionable insights for both clinicians and researchers. Traditional survival models often fail to capture non-linear interactions, while modern deep learning approaches, though powerful, are limited by poor interpretability. We propose a Pipeline for Interpretable Survival Analysis (PISA) - a pipeline that provides multiple survival analysis models that trade off complexity and performance. Using multiple-feature, multi-objective feature engineering, PISA transforms patient characteristics and time-to-event data into multiple survival analysis models, providing valuable insights into the survival prediction task. Crucially, every model is converted into simple patient stratification flowcharts supported by Kaplan-Meier curves, whilst not compromising on performance. While PISA is model-agnostic, we illustrate its flexibility through applications of Cox regression and shallow survival trees, the latter avoiding proportional hazards assumptions. Applied to two clinical benchmark datasets, PISA produced interpretable survival models and intuitive stratification flowcharts whilst achieving state-of-the-art performances. Revisiting a prior departmental study further demonstrated its capacity to automate survival analysis workflows in real-world clinical research.


KM-GPT: An Automated Pipeline for Reconstructing Individual Patient Data from Kaplan-Meier Plots

Zhao, Yao, Sun, Haoyue, Ding, Yantian, Xu, Yanxun

arXiv.org Machine Learning

Reconstructing individual patient data (IPD) from Kaplan-Meier (KM) plots provides valuable insights for evidence synthesis in clinical research. However, existing approaches often rely on manual digitization, which is error-prone and lacks scalability. To address these limitations, we develop KM-GPT, the first fully automated, AI-powered pipeline for reconstructing IPD directly from KM plots with high accuracy, robustness, and reproducibility. KM-GPT integrates advanced image preprocessing, multi-modal reasoning powered by GPT-5, and iterative reconstruction algorithms to generate high-quality IPD without manual input or intervention. Its hybrid reasoning architecture automates the conversion of unstructured information into structured data flows and validates data extraction from complex KM plots. To improve accessibility, KM-GPT is equipped with a user-friendly web interface and an integrated AI assistant, enabling researchers to reconstruct IPD without requiring programming expertise. KM-GPT was rigorously evaluated on synthetic and real-world datasets, consistently demonstrating superior accuracy. To illustrate its utility, we applied KM-GPT to a meta-analysis of gastric cancer immunotherapy trials, reconstructing IPD to facilitate evidence synthesis and biomarker-based subgroup analyses. By automating traditionally manual processes and providing a scalable, web-based solution, KM-GPT transforms clinical research by leveraging reconstructed IPD to enable more informed downstream analyses, supporting evidence-based decision-making.


Federated Survival Analysis with Node-Level Differential Privacy: Private Kaplan-Meier Curves

Veeraragavan, Narasimha Raghavan, Nygård, Jan Franz

arXiv.org Artificial Intelligence

We investigate how to calculate Kaplan-Meier survival curves across multiple health-care jurisdictions while protecting patient privacy with node-level differential privacy. Each site discloses its curve only once, adding Laplace noise whose scale is determined by the length of the common time grid; the server then averages the noisy curves, so the overall privacy budget remains unchanged. We benchmark four one-shot smoothing techniques: Discrete Cosine Transform, Haar Wavelet shrinkage, adaptive Total-Variation denoising, and a parametric Weibull fit on the NCCTG lung-cancer cohort under five privacy levels and three partition scenarios (uniform, moderately skewed, highly imbalanced). Total-Variation gives the best mean accuracy, whereas the frequency-domain smoothers offer stronger worst-case robustness and the Weibull model shows the most stable behaviour at the strictest privacy setting. Across all methods the released curves keep the empirical log-rank type-I error below fifteen percent for privacy budgets of 0.5 and higher, demonstrating that clinically useful survival information can be shared without iterative training or heavy cryptography.


Targeted Deep Architectures: A TMLE-Based Framework for Robust Causal Inference in Neural Networks

Li, Yi, Mccoy, David, Gunter, Nolan, Lee, Kaitlyn, Schuler, Alejandro, van der Laan, Mark

arXiv.org Artificial Intelligence

Modern deep neural networks are powerful predictive tools yet often lack valid inference for causal parameters, such as treatment effects or entire survival curves. While frameworks like Double Machine Learning (DML) and Targeted Maximum Likelihood Estimation (TMLE) can debias machine-learning fits, existing neural implementations either rely on "targeted losses" that do not guarantee solving the efficient influence function equation or computationally expensive post-hoc "fluctuations" for multi-parameter settings. We propose Targeted Deep Architectures (TDA), a new framework that embeds TMLE directly into the network's parameter space with no restrictions on the backbone architecture. Specifically, TDA partitions model parameters - freezing all but a small "targeting" subset - and iteratively updates them along a targeting gradient, derived from projecting the influence functions onto the span of the gradients of the loss with respect to weights. This procedure yields plug-in estimates that remove first-order bias and produce asymptotically valid confidence intervals. Crucially, TDA easily extends to multi-dimensional causal estimands (e.g., entire survival curves) by merging separate targeting gradients into a single universal targeting update. Theoretically, TDA inherits classical TMLE properties, including double robustness and semiparametric efficiency. Empirically, on the benchmark IHDP dataset (average treatment effects) and simulated survival data with informative censoring, TDA reduces bias and improves coverage relative to both standard neural-network estimators and prior post-hoc approaches. In doing so, TDA establishes a direct, scalable pathway toward rigorous causal inference within modern deep architectures for complex multi-parameter targets.


Deep Survival Analysis in Multimodal Medical Data: A Parametric and Probabilistic Approach with Competing Risks

Garrido, Alba, Almodóvar, Alejandro, Apellániz, Patricia A., Parras, Juan, Zazo, Santiago

arXiv.org Artificial Intelligence

Accurate survival prediction is critical in oncology for prognosis and treatment planning. Traditional approaches often rely on a single data modality, limiting their ability to capture the complexity of tumor biology. To address this challenge, we introduce a multimodal deep learning framework for survival analysis capable of modeling both single and competing risks scenarios, evaluating the impact of integrating multiple medical data sources on survival predictions. We propose SAMVAE (Survival Analysis Multimodal Variational Autoencoder), a novel deep learning architecture designed for survival prediction that integrates six data modalities: clinical variables, four molecular profiles, and histopathological images. SAMVAE leverages modality specific encoders to project inputs into a shared latent space, enabling robust survival prediction while preserving modality specific information. Its parametric formulation enables the derivation of clinically meaningful statistics from the output distributions, providing patient-specific insights through interactive multimedia that contribute to more informed clinical decision-making and establish a foundation for interpretable, data-driven survival analysis in oncology. We evaluate SAMVAE on two cancer cohorts breast cancer and lower grade glioma applying tailored preprocessing, dimensionality reduction, and hyperparameter optimization. The results demonstrate the successful integration of multimodal data for both standard survival analysis and competing risks scenarios across different datasets. Our model achieves competitive performance compared to state-of-the-art multimodal survival models. Notably, this is the first parametric multimodal deep learning architecture to incorporate competing risks while modeling continuous time to a specific event, using both tabular and image data.


In-Training Multicalibrated Survival Analysis for Healthcare via Constrained Optimization

Suttaket, Thiti, Kok, Stanley

arXiv.org Artificial Intelligence

Survival analysis is an important problem in healthcare because it models the relationship between an individual's covariates and the onset time of an event of interest (e.g., death). It is important for survival models to be well-calibrated (i.e., for their predicted probabilities to be close to ground-truth probabilities) because badly calibrated systems can result in erroneous clinical decisions. Existing survival models are typically calibrated at the population level only, and thus run the risk of being poorly calibrated for one or more minority subpopulations. We propose a model called GRADUATE that achieves multicalibration by ensuring that all subpopulations are well-calibrated too. GRADUATE frames multicalibration as a constrained optimization problem, and optimizes both calibration and discrimination in-training to achieve a good balance between them. We mathematically prove that the optimization method used yields a solution that is both near-optimal and feasible with high probability. Empirical comparisons against state-of-the-art baselines on real-world clinical datasets demonstrate GRADUATE's efficacy. In a detailed analysis, we elucidate the shortcomings of the baselines vis-a-vis GRADUATE's strengths.