*Result*: Fitting high-dimensional mixture cure models using the hdcuremodelsR package.

Title:
Fitting high-dimensional mixture cure models using the hdcuremodelsR package.
Authors:
Archer KJ; The Ohio State University, Division of Biostatistics, College of Public Health, Columbus, 43210, OH, United States. Electronic address: archer.43@osu.edu., Fu H; Google, Inc, 600 Amphitheatre Parkway, Mountain View, 94043, CA, United States.
Source:
Computer methods and programs in biomedicine [Comput Methods Programs Biomed] 2026 Mar; Vol. 276, pp. 109212. Date of Electronic Publication: 2025 Dec 31.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Scientific Publishers Country of Publication: Ireland NLM ID: 8506513 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7565 (Electronic) Linking ISSN: 01692607 NLM ISO Abbreviation: Comput Methods Programs Biomed Subsets: MEDLINE
Imprint Name(s):
Publication: Limerick : Elsevier Scientific Publishers
Original Publication: Amsterdam : Elsevier Science Publishers, c1984-
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Grant Information:
R01 LM013879 United States LM NLM NIH HHS
Contributed Indexing:
Keywords: LASSO; Penalized; R; Regularized; Survival
Entry Date(s):
Date Created: 20260103 Date Completed: 20260121 Latest Revision: 20260122
Update Code:
20260130
PubMed Central ID:
PMC12809250
DOI:
10.1016/j.cmpb.2025.109212
PMID:
41483547
Database:
MEDLINE

*Further Information*

*Background and Objective: Time-to-event outcomes are often of interest in biomedical studies. When the dataset includes long-term survivors or subjects who will not experience the event of interest, mixture cure models (MCMs) should be fit. Further, it is clinically relevant to identify molecular features from high-throughput assays that are associated with time-to-event outcomes, both to elucidate important pathways and to identify molecular features that may be therapeutic targets or for developing improved risk stratification systems. Herein, we describe our hdcuremodelsR package that can be used to model right-censored time-to-event data when a cured fraction is present and the predictor space is high-dimensional.
Methods: We implemented two different optimization methods, the expectation-maximization and generalized monotone incremental forward stagewise algorithms, for fitting high-dimensional penalized Weibull, exponential, and Cox mixture cure models. Cross-validation functions for each optimization method are provided that can be run with or without controlling the false discovery rate. The modeling functions are flexible in that there is no requirement for the predictors to be the same in the incidence and latency components of the model. The package also includes functions for testing mixture cure modeling assumptions, evaluating performance, and generic functions that can be used to extract meaningful results.
Results: We demonstrate fitting a high-dimensional penalized mixture cure model to an acute myeloid leukemia dataset, which had strong predictive performance on an independent test set.
Conclusion: Our hdcuremodels package fits penalized mixture cure models that can accommodate datasets where the number of predictors exceeds the sample size.
(Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)*

*Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kellie J. Archer reports financial support was provided by National Institutes of Health National Library of Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*