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CoxKAN: Kolmogorov-Arnold networks for interpretable, high-performance survival analysis.

MOTIVATION: Survival analysis is a branch of statistics that is crucial in medicine for modeling the time to critical events such as death or relapse, in order to improve treatment strategies and patient outcomes. Selecting survival models often involves a trade-off between performance and interpretability; deep learning models offer high performance but lack the transparency of more traditional approaches. This poses a significant issue in medicine, where practitioners are reluctant to use black-box models for critical patient decisions. RESULTS: We introduce CoxKAN, a Cox proportional hazards Kolmogorov-Arnold Network for interpretable, high-performance survival analysis. Kolmogorov-Arnold Networks (KANs) were recently proposed as an interpretable and accurate alternative to multi-layer perceptrons. We evaluated CoxKAN on four synthetic and nine real datasets, including five cohorts with clinical data and four with genomics biomarkers. In synthetic experiments, CoxKAN accurately recovered interpretable hazard function formulae and excelled in automatic feature selection. Evaluations on real datasets showed that CoxKAN consistently outperformed the traditional Cox proportional hazards model (by up to 4% in C-index) and matched or surpassed the performance of deep learning-based models. Importantly, CoxKAN revealed complex interactions between predictor variables and uncovered symbolic formulae, which are key capabilities that other survival analysis methods lack, to provide clear insights into the impact of key biomarkers on patient risk. AVAILABILITY AND IMPLEMENTATION: CoxKAN is available at GitHub and Zenodo.

Humans

Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the United States.

Population-based incidence data on nasopharyngeal carcinomas (NPC) from the Surveillance, Epidemiology and End Results program in the United States were examined for the years 1973-1986. The 1,645 cases showed incidence rates varying according to ethnic origin, with chinese having the highest, followed by Filipinos, Blacks and Whites. In females the incidence was about half of that seen in males, in each of these groups. There was no evidence of changes in incidence rates during the study period. An analysis of survival with NPC was undertaken using hazard function regression models to allow for control of multiple variables. Survival was found to be independently influenced by age and stage at diagnosis, histologic type, grade and sex. Significant ethnic differences in survival remained after adjustment for these factors, with Chinese surviving longest followed by Filipinos, Whites and Blacks. These difference in survival remained after control for the variation in population-wide mortality rates associated with age, ethnicity, sex and calendar year. We present evidence that survival has improved for this disease over time.

Adolescent

Repeated assessment of risk factors in survival analysis.

Regression models for survival data with time-dependent covariates are considered. We review estimation in the Cox regression model and discuss problems in connection with data requirements for the analysis, with interpretation of results and with prediction based on such a model. In particular, we discuss how the latter problems may be approached within an extended (Markov process) model. A clinical trial in liver cirrhosis is used for illustration.

Clinical Trials as Topic

[Description and survival analysis of 401 cases of AIDS in Madrid].

A descriptive trial and an analysis of global survival, in relation to the different risk's groups and the type of clinical onset, was carried out in 401 patient diagnosed of AIDS in our hospital form 1984 to 1990. The males with addiction to parenteral drugs account for the most numerous group. Extrapulmonary tuberculosis was the most frequent presentation. During the period mentioned before, the survival distribution using the Kaplan-Meyer method was 52% for 12 months (SE = 0.0347). The survival rate was significantly higher (p less than 0.01) in those patients who presented an extrapulmonary tuberculosis as an onset of his disease.

Acquired Immunodeficiency Syndrome

Detection of significant demographic differences between subpopulations of prehispanic Maya from Copan, Honduras, by survival analysis.

Heterogeneity and small sample size are problems that affect many paleodemographic studies. The former can cause the overall distribution of age at death to be an amalgam that does not accurately reflect the distributions of any of the groups composing the heterogeneous population. The latter can make it difficult to separate significant from nonsignificant demographic differences between groups. Survival analysis, a methodology that involves the survival distribution function and various regression models, can be applied to distributions of age at death in order to reveal statistically significant demographic differences and to control for heterogeneity. Survival analysis was used on demographic data from a heterogeneous sample of skeletons of low status Maya who lived in and around Copan, Honduras, between A.D. 400 and 1200. Results contribute to understanding the collapse of Classic Maya civilization.

Age Factors

Importance of district of residence and known primary site for bowel cancer survival: analysis of data from Wessex Cancer Registry.

STUDY OBJECTIVE: The aim was to compare survival with colon and rectal cancer across the 10 districts of Wessex taking into account the age and sex of the individual. DESIGN: The study was based on registrations on the Wessex Cancer Registry between 1979 and 1984 with colon and rectal cancer. Survival up to 31 December 1986 was examined using a Cox regression model; individuals surviving to the end of the follow up period were treated as censored in the analysis. Survival was examined in the first fortnight, the first month, and the first six months after registration separately. PARTICIPANTS: The data comprised 6239 residents of the Wessex Region who had been diagnosed with colon cancer and 3203 residents diagnosed with rectal cancer. For 140 cases survival data or age were missing and these cases were excluded. MEASUREMENTS AND MAIN RESULTS: Results are presented in the format of a league table giving the order of districts from lowest to highest survival rates. No significant differences in survival are found between districts in relation to rectal cancer. We find that one or two districts have consistently high or low survival rates with colon cancer in various periods of follow up, but cannot differentiate between the districts in the centre of the list. Site unspecified is considered as an explanatory variable; it is more predictive than district, and it approaches the importance of age in explaining survival with colon cancer. CONCLUSIONS: There are significant differences in survival with colon cancer between districts; however data on stage at registration are not available and we are unable to say whether the differences in survival are due to differences in stage at diagnosis or differences in survival with similar stage at diagnosis. We found that cases where the site of the cancer within the colon was not recorded on the register have significantly lower survival, and we suggest that site unspecified may be related to stage at diagnosis.

Age Factors

Revision total knee arthroplasty. A survival analysis.

The results of revision total knee arthroplasty (TKA) have been documented reasonably well in the literature. It is notable, however, that none of these reports have used the technique known as survival analysis to compare virgin and revision arthroplasties. This technique has an advantage over conventional analyses because it does not exclude patient data for inadequate follow-up study or patient death. In this study, survival analysis was applied to 37 revision TKAs performed exclusively by the senior author. With failure defined as removal of the prosthesis, revision surgeries experienced a 97.0% survival rate at 6 years. The secondary arthroplasty demonstrated a significantly lower survival rate than the index procedure over a period of approximately 6 years.

Actuarial Analysis

Survival analysis of octogenarian patients with coronary artery disease managed by elective coronary artery bypass surgery versus conventional medical treatment.

BACKGROUND: In view of the increasing age of the U.S. population, the use of coronary artery bypass surgery in the management of the elderly patients with coronary artery disease needs to be better defined. METHODS AND RESULTS: To evaluate the effects of medical and surgical therapy on octogenarian patients with coronary artery disease in our institution, we retrospectively reviewed 177 consecutive octogenarians who underwent cardiac catheterization over a 5-year period. Sixty-five of these patients were found to have significant coronary artery disease without severe valvular disease. Elective coronary artery bypass surgery was performed in 36 patients, whereas 29 patients were continued on maximization of medical therapy and not referred to the surgical service. Left ventricular ejection fractions (LVEF) were similar for the two groups, whereas the surgical patients had slightly higher average number of diseased coronary vessels and slightly higher levels of angina. Univariate survival analysis of 20 variables, including the choice of medical versus surgical treatment and the associated conditions, was performed by Mantel-Cox testing of the paired Kaplan-Meier product limit survival curves stratified by the subgroups of each variable. The variables found to be significant were then included in a multivariate survival analysis using the Cox proportional hazards regression model. The treatment choice, LVEF, level of angina, and presence of any aortic and/or mitral valvular disease at the time of cardiac catheterization were found to be independent prognostic indicators of survival in the follow-up period of 26 +/- 16 months. The 3-year probability of survival rates for the surgical patients and medical patients were 77.4% and 55.2%, respectively (p = 0.0294). The New York Heart Association functional class of the surgical group decreased significantly from a mean preoperative level of 3.4 +/- 0.5 to a mean level of 1.2 +/- 0.6 at the follow-up interview (p < 0.01), whereas it did not significantly change for the medical group from a baseline mean level of 2.8 +/- 1.3 to a mean follow-up level of 2.5 +/- 1.0. CONCLUSIONS: We conclude that coronary artery bypass surgery provided improved long-term survival and functional benefit compared with conventional medical treatment in a small group of octogenarian patients in our institution.

Aged

[AIDS: descriptive study and survival analysis of the 1st 40 cases].

AIM: To analyze the epidemiologic and clinical features, the survival as well as length of stay of the first 40 AIDS cases seen at the internal Medicine Department of the Virgen de la Arrixaca Hospital (Murcia, Spain). METHODS: Prospective study from September 1988 through July 1991. AIDS criteria used were the CDC (1987) ones. The survival analysis was performed using the Kaplan-Meier method. RESULTS: Thirty-four patients were male (85%) and six female (15%), with a mean age of 39 years. Eighteen (45%) were homo or bisexual, 11 drug addicts (27.5%), 8 (20%) had sexual contacts with prostitutes and/or drug addicts. Two patients were recipients of blood products and in one case no risk could be determined. Opportunistic infections were the first AIDS criteria in 75% of cases. Among the most frequent are P. carinii pneumonia (17.5%), CNS toxoplasmosis (15%) and cryptosporidiosis (12.5%). In 20% of cases a Kaposi's sarcoma developed. The probability of survival after three months was 91% +/- 9.6, at 7 months 79.5% +/- 15.0 and at 15 months 72.5 +/- 18. Overall, 90% of patients had at least one hospital admission, and 27.7% were hospitalized for 50% of more of their survival time. CONCLUSIONS: We recorded an increased number of AIDS cases since 1988, being most of them homo-bisexual male patients, with opportunistic infections as first manifestation. We noticed also high proportion of cases of heterosexual transmission.

Acquired Immunodeficiency Syndrome

Foundation model based multimodal transformer framework for survival analysis in HER2 stratified breast cancer.

Objective. To improve survival prediction for HER2-positive breast cancer by integrating histopathological, molecular, and clinical data using a multimodal transformer framework.Approach. We propose a multimodal transformer framework for breast cancer survival prediction using HER2 stratified (SurvMBC), a foundation model-enhanced architecture that fuses three data modalities: whole-slide images, clinical narratives, and molecular features. Tumor microenvironment features are extracted using a pathology language and image pre-training (PLIP), clinical narratives are processed with BioBERT, and miRNA expression plus DNA methylation data are embedded using Gen2Vec. These representations are integrated through a cross-modal transformer with attention mechanisms for survival prediction.Main results. The model was evaluated on 1,095 HER2-positive breast cancer patients from The Cancer Genome Atlas. SurvMBC achieved a concordance index (C-index) of 0.857 (95% CI: 0.834, 0.880), a low integrated Brier score, and a strong inverse negative binomial log-likelihood. Risk stratification based on model outputs significantly separated high- and low-risk groups (log-rankp< 0.01) and showed strong associations with tumor stage, grade, and hormone receptor status (allp< 0.05).Significance. SurvMBC demonstrates the effectiveness of multimodal fusion in addressing tumor heterogeneity and improving prognostic accuracy. The attention-based integration enables context-aware learning of survival-relevant features across modalities, supporting individualized risk stratification and risk-adaptive treatment planning for HER2 stratified breast cancer patients.

Breast Neoplasms

The Attenborough and Gallannaugh knee prostheses for total knee arthroplasty. A comparison and survival analysis.

The characteristic feature of the Attenborough knee prosthesis was a stabilizing link rod, designed to act in place of the cruciate ligaments and to supplement the function of the collateral ligaments when damaged by disease. However, the reported long-term results obtained with this prosthesis have not been satisfactory, and survival analysis of 505 arthroplasties in which this prosthesis was used demonstrates a cumulative 14-year success rate of only 44.9%. In 1982, a new design incorporating the link rod was developed and the results of 149 knees in which this prosthesis was used show a cumulative seven-year success rate of 98.4%, compared with 70.1% in the Attenborough series. The clinical results of the Gallannaugh series are presented in this study. Knee function has been separated from patient activity, the patients being categorized in groups according to their physical state. Thus, the result of the knee operation can be assessed even in those disabled by age and infirmity. The Gallannaugh prosthesis is of particular value in circumstances where the use of an unconstrained prosthesis would be impractical.

Aged

Applications of survival analysis to aging research.

Many research questions in aging research treat time as the outcome variable. Researchers ask how much time must pass before a specific type of change or event occurs, and whether these times differ by characteristics of the subjects' background, training and treatment. Because of serious technical problems that arise when analyzing duration data, specially derived statistical methods--the methods of survival analysis--are required to answer the questions. In this paper, we introduce the conceptual framework of these new methodologies for analyzing duration data. We begin by identifying the types of research question that might appropriately treat time as an outcome. We then describe the new statistical methods for addressing such questions, provide a broad overview of their application, and identify relevant published sources containing additional background and technical information.

Aging

Efficacy of lung cancer screening; comparison of results from a case-control study and a survival analysis. The Japanese Lung Cancer Screening Research Group.

A case-control study to evaluate the efficacy of lung cancer screening conducted by us showed that lung cancer screening may reduce the mortality of the disease up to 28%. Assuming this efficacy is unbiased, and that the screening rate is 51.6%, which was observed in the control group in the above study, the number of lung cancer deaths prevented by screening in the study period was calculated to be 47 for males and females combined. In the same study population, screen-detected lung cancer patients (N = 207) in the same study period were followed and the 7-year survival rate (46.9%) was compared to the 5-year survival rate (11.3%) obtained by the Osaka Cancer Registry, in which screen-detected lung cancer patients were only 1.8%. The number of lung cancer deaths prevented by screening, estimated by the difference in the above two survival rates, was 74 (95% confidence interval; 55-93). The number of lung cancer deaths prevented by screening estimated from the case-control study was significantly lower than that estimated from the survival analysis. This indicates that the efficacy of lung cancer screening estimated by the case-control study was within the range that could be explained by the actual long-term survivors among the screen-detected patients in the study population.

Adult

Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis.

Smooth-walled silicone implants have been widely used in breast surgery. Capsular contracture, causing undesirable firmness and spherical deformity, has been a common problem. Recent studies suggest that polyurethane-covered breast implants are associated with a lower incidence of capsular contracture. The statistical methodology employed in some of these studies, however, may be subject to criticism. Between July of 1984 and June of 1990 (72 months), 427 polyurethane breast implants were used in 279 patients and 439 smooth prostheses were used in 250 patients for a variety of aesthetic and reconstructive procedures. The occurrence of capsular contracture was carefully monitored and then analyzed using the Kaplan-Meier method of survival analysis. This method is particularly well suited to analysis of these types of clinical data because it allows for the fact that contractures occur at varying intervals after surgery and that follow-up of patients is incomplete. The probability of capsular contracture with smooth-walled prostheses was found to be significantly greater than with polyurethane-covered implants in each group of patients studied (p less than 0.05). Other complications occurred at a similar rate regardless of prosthesis type. This study supports the belief that polyurethane breast implants have a lower contracture rate; furthermore, it introduces the Kaplan-Meier method for analyzing the outcome of alternative plastic surgical therapies.

Breast

Polygenic risk factors for comorbid diagnoses in individuals with substance use disorders: A phenome-wide survival analysis.

OBJECTIVE: Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome-wide association studies (PheWASs). However, PheWASs are largely cross-sectional, limiting our understanding of whether diagnoses predate the development of an SUD. We characterize whether polygenic scores (PGSs) are associated with time to comorbid diagnoses in electronic health records (EHR) after the first documented SUD diagnosis. METHODS: Using data from All of Us (N&#xa0;=&#xa0;393,596), we explored: (1) whether social determinants of health (SDoHs) are associated with lifetime risk of SUD (N cases&#xa0;=&#xa0;42,568) and (2) within a subset those with a diagnosed SUD and available genetic data SUD (N&#xa0;=&#xa0;21,357), whether PGS for alcohol use disorders, cannabis use disorders, depression, externalizing, posttraumatic stress disorder, and schizophrenia were associated with subsequent diagnoses via a phenome-wide survival analysis. RESULTS: Multiple SDoHs were associated with lifetime SUD diagnosis, with annual household income having the largest overall associations (e.g. <$10&#xa0;K annually vs $100&#xa0;K-$150&#xa0;K annually: OR&#xa0;=&#xa0;4.18; 95% CI&#xa0;=&#xa0;3.92, 4.45). There were 86 phenome-wide significant PGS associations with subsequent diagnoses across various bodily systems. PGSs for alcohol use disorders, posttraumatic stress disorder, and schizophrenia were each associated with time to their respective diagnoses. CONCLUSIONS: Social determinants, especially those related to income, have profound associations with lifetime SUD risk. Additionally, PGSs for psychiatric conditions are associated with multiple post-SUD diagnoses within those with a SUD, suggesting PGS may capture information beyond lifetime risk, including timing and severity of comorbidities related to SUD.

Humans

The accelerated failure time model: a useful alternative to the Cox regression model in survival analysis.

For the past two decades the Cox proportional hazards model has been used extensively to examine the covariate effects on the hazard function for the failure time variable. On the other hand, the accelerated failure time model, which simply regresses the logarithm of the survival time over the covariates, has seldom been utilized in the analysis of censored survival data. In this article, we review some newly developed linear regression methods for analysing failure time observations. These procedures have sound theoretical justification and can be implemented with an efficient numerical method. The accelerated failure time model has an intuitive physical interpretation and would be a useful alternative to the Cox model in survival analysis.

Proportional Hazards Models

Interaction of cytotoxic agents: a rule-based system for computer-assisted cell survival analysis.

The actual effectiveness of environmental noxious agents or anticancer drugs can be fully determined only by knowing if the effects (in the present case, the cytotoxic effects) induced by a given agent are enhanced by exposure to another (or other) agent(s). Given a certain combination of agents, it is possible to distinguish three types of interaction: (a) zero interaction or additivity; (b) positive interaction or synergism; and (c) negative interaction or antagonism. In this work, the methodological problems involved in evaluating the type and level of interaction between biologically active agents are discussed and an "intelligent" approach to the problem is proposed. In particular, a prototype of a computer-assisted rule based system, named CISA (Cytotoxic Interaction and Survival Analysis), designed in a KES environment (Knowledge Engineering System) and implemented on a personal computer, is described. By constructing isoboles based on experimental cell survival data and taking into account the relative confidence intervals, the system can indicate the appropriate combinations of dosages to be tested and finally determine the type and level of interaction. The system, which represents an attempt to administer "intelligently" the experimental data, is therefore able to identify the best strategy of analysis, to carry out the data processing and to offer suggestions to the investigator about the usefulness of the data and the planning of further experiments.

Animals