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Published in: BMC Medical Informatics and Decision Making 1/2019

Open Access 01-12-2019 | Bone Metastasis | Research article

Modelling cancer outcomes of bone metastatic patients: combining survival data with N-Telopeptide of type I collagen (NTX) dynamics through joint models

Authors: Hugo Loureiro, Eunice Carrasquinha, Irina Alho, Arlindo R. Ferreira, Luís Costa, Alexandra M. Carvalho, Susana Vinga

Published in: BMC Medical Informatics and Decision Making | Issue 1/2019

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Abstract

Background

Joint models (JM) have emerged as a promising statistical framework to concurrently analyse survival data and multiple longitudinal responses. This is particularly relevant in clinical studies where the goal is to estimate the association between time-to-event data and the biomarkers evolution. In the context of oncological data, JM can indeed provide interesting prognostic markers for the event under study and thus support clinical decisions and treatment choices. However, several problems arise when dealing with this type of data, such as the high-dimensionality of the covariates space, the lack of knowledge about the function structure of the time series and the presence of missing data, facts that may hamper the accurate estimation of the JM.

Methods

We propose to apply JM for the analysis of bone metastatic patients and infer the association of their survival with several covariates, in particular the N-Telopeptide of Type I Collagen (NTX) dynamics. This biomarker has been identified as a relevant prognostic factor in patients with metastatic cancer, but only using static information in some specific time points.

Results

We extended this analysis using the full NTX time series for a larger cohort of patients with bone metastasis, and compared the results obtained by the JM and the extended Cox regression model. Imputation based on fuzzy clustering was used to deal with missing values and several functions for NTX evolution were compared, such as rational, exponential and cubic splines.

Conclusions

The JM obtained confirm the association between NTX values and patients’ response, attesting the importance of this time series, and additionally provide a deep understanding of the key survival covariates.
Literature
1.
go back to reference Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. Journal of the American Statistical Association. J Am Stat Assoc. 1958; 53(282):457–81.CrossRef Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. Journal of the American Statistical Association. J Am Stat Assoc. 1958; 53(282):457–81.CrossRef
2.
go back to reference Cox DR. Regression Models and Life-Tables. J R Stat Soc Ser B (Methodol). 1972; 34(2):187–220. Cox DR. Regression Models and Life-Tables. J R Stat Soc Ser B (Methodol). 1972; 34(2):187–220.
5.
go back to reference Rizopoulos D. Joint Models for Longitudinal and Time-to-Event Data: With Applications in R, 1st edn. Boca Raton: CRC Press; 2012, p. 274.CrossRef Rizopoulos D. Joint Models for Longitudinal and Time-to-Event Data: With Applications in R, 1st edn. Boca Raton: CRC Press; 2012, p. 274.CrossRef
9.
go back to reference Yu M, Law NJ, Taylor JMG, Sandler HM. Joint Longitudinal-Survival-Cure Models and their Application to Prostate Cancer. Stat Sin. 2004; 14:835–62. Yu M, Law NJ, Taylor JMG, Sandler HM. Joint Longitudinal-Survival-Cure Models and their Application to Prostate Cancer. Stat Sin. 2004; 14:835–62.
15.
go back to reference Diggle PJ, Heagerty P, Liang K-Y, Zeger SL. Analysis of Longitudinal Data, 2nd edn. Oxford: Oxford University Press; 2002, p. 379. Diggle PJ, Heagerty P, Liang K-Y, Zeger SL. Analysis of Longitudinal Data, 2nd edn. Oxford: Oxford University Press; 2002, p. 379.
24.
Metadata
Title
Modelling cancer outcomes of bone metastatic patients: combining survival data with N-Telopeptide of type I collagen (NTX) dynamics through joint models
Authors
Hugo Loureiro
Eunice Carrasquinha
Irina Alho
Arlindo R. Ferreira
Luís Costa
Alexandra M. Carvalho
Susana Vinga
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Bone Metastasis
Published in
BMC Medical Informatics and Decision Making / Issue 1/2019
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-018-0728-1

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