*Result*: Fitting high-dimensional mixture cure models using the hdcuremodelsR package.
Original Publication: Amsterdam : Elsevier Science Publishers, c1984-
J Stat Softw. 2010;33(1):1-22. (PMID: 20808728)
J Comput Graph Stat. 2018;27(1):48-58. (PMID: 29861617)
Stat Methods Med Res. 2023 Dec;32(12):2405-2422. (PMID: 37937365)
Stat Med. 2023 Oct 15;42(23):4111-4127. (PMID: 37503905)
Comput Methods Programs Biomed. 2012 Dec;108(3):1255-60. (PMID: 23017250)
Stat Methods Med Res. 2022 Nov;31(11):2164-2188. (PMID: 35912505)
J Clin Epidemiol. 1991;44(12):1327-40. (PMID: 1753264)
Comput Methods Programs Biomed. 2022 Nov;226:107125. (PMID: 36126436)
J Biopharm Stat. 2017;27(6):918-932. (PMID: 28324665)
Stat Comput. 2024 Aug;34(4):. (PMID: 39776468)
Comput Methods Programs Biomed. 2007 Feb;85(2):173-80. (PMID: 17157948)
Lifetime Data Anal. 2023 Jul;29(3):608-627. (PMID: 36890338)
J Hematol Oncol. 2024 May 3;17(1):28. (PMID: 38702786)
Stat Med. 2022 Sep 30;41(22):4340-4366. (PMID: 35792553)
Stat Methods Med Res. 2022 Nov;31(11):2037-2053. (PMID: 35754373)
BMC Med Res Methodol. 2023 Mar 25;23(1):70. (PMID: 36966273)
Pharm Stat. 2014 Nov-Dec;13(6):357-63. (PMID: 25044997)
Artif Intell Med. 2024 Apr;150:102817. (PMID: 38553157)
Biom J. 2018 Jul;60(4):780-796. (PMID: 29733452)
Stat Med. 1999 Feb 28;18(4):441-54. (PMID: 10070685)
Biometrics. 2021 Dec;77(4):1289-1302. (PMID: 32869288)
*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.*