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Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma
Retroperitoneal sarcoma (RPS) is a rare malignancy which can be difficult to manage due to the variety of clinical behaviors. In this study, we aimed to develop a parametric modeling framework to quantify the relationship between postoperative dynamics of several biomarkers and overall/progression‐f...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469699/ https://www.ncbi.nlm.nih.gov/pubmed/35758865 http://dx.doi.org/10.1002/psp4.12835 |
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author | Yao, Ye Wang, Zhen Yong, Ling Yao, Qingyu Tian, Xiuyun Wang, Tianyu Yang, Qirui Hao, Chunyi Zhou, Tianyan |
author_facet | Yao, Ye Wang, Zhen Yong, Ling Yao, Qingyu Tian, Xiuyun Wang, Tianyu Yang, Qirui Hao, Chunyi Zhou, Tianyan |
author_sort | Yao, Ye |
collection | PubMed |
description | Retroperitoneal sarcoma (RPS) is a rare malignancy which can be difficult to manage due to the variety of clinical behaviors. In this study, we aimed to develop a parametric modeling framework to quantify the relationship between postoperative dynamics of several biomarkers and overall/progression‐free survival of RPS. One hundred seventy‐four patients with RPS who received surgical resection with curative intent at the Peking University Cancer Hospital Sarcoma Center were retrospectively included. Potential prognostic factors were preliminarily identified. Longitudinal analyses of body mass index (BMI), serum total protein (TP), and white blood cells (WBCs) were performed using nonlinear mixed effects models. The impacts of time‐varying and time‐invariant predictors on survival were investigated by parametric time‐to‐event (TTE) models. The majority of patients experienced decline in BMI, recovery of TP, as well as transient elevation in WBC counts after surgery, which significantly correlated with survival. An indirect‐response model incorporating surgery effect described the fluctuation in percentage BMI. The recovery of TP was captured by a modified Gompertz model, and a semimechanistic model was selected for WBCs. TTE models estimated that the daily cumulative average of predicted BMI and WBC, the seventh‐day TP, as well as certain baseline variables, were significant predictors of survival. Model‐based simulations were performed to examine the clinical significance of prognostic factors. The current work quantified the individual trajectories of prognostic biomarkers in response to surgery and predicted clinical outcomes, which would constitute an additional strategy for disease monitoring and intervention in postoperative RPS. |
format | Online Article Text |
id | pubmed-9469699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94696992022-09-27 Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma Yao, Ye Wang, Zhen Yong, Ling Yao, Qingyu Tian, Xiuyun Wang, Tianyu Yang, Qirui Hao, Chunyi Zhou, Tianyan CPT Pharmacometrics Syst Pharmacol Research Retroperitoneal sarcoma (RPS) is a rare malignancy which can be difficult to manage due to the variety of clinical behaviors. In this study, we aimed to develop a parametric modeling framework to quantify the relationship between postoperative dynamics of several biomarkers and overall/progression‐free survival of RPS. One hundred seventy‐four patients with RPS who received surgical resection with curative intent at the Peking University Cancer Hospital Sarcoma Center were retrospectively included. Potential prognostic factors were preliminarily identified. Longitudinal analyses of body mass index (BMI), serum total protein (TP), and white blood cells (WBCs) were performed using nonlinear mixed effects models. The impacts of time‐varying and time‐invariant predictors on survival were investigated by parametric time‐to‐event (TTE) models. The majority of patients experienced decline in BMI, recovery of TP, as well as transient elevation in WBC counts after surgery, which significantly correlated with survival. An indirect‐response model incorporating surgery effect described the fluctuation in percentage BMI. The recovery of TP was captured by a modified Gompertz model, and a semimechanistic model was selected for WBCs. TTE models estimated that the daily cumulative average of predicted BMI and WBC, the seventh‐day TP, as well as certain baseline variables, were significant predictors of survival. Model‐based simulations were performed to examine the clinical significance of prognostic factors. The current work quantified the individual trajectories of prognostic biomarkers in response to surgery and predicted clinical outcomes, which would constitute an additional strategy for disease monitoring and intervention in postoperative RPS. John Wiley and Sons Inc. 2022-07-04 2022-09 /pmc/articles/PMC9469699/ /pubmed/35758865 http://dx.doi.org/10.1002/psp4.12835 Text en © 2022 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Yao, Ye Wang, Zhen Yong, Ling Yao, Qingyu Tian, Xiuyun Wang, Tianyu Yang, Qirui Hao, Chunyi Zhou, Tianyan Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
title | Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
title_full | Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
title_fullStr | Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
title_full_unstemmed | Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
title_short | Longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
title_sort | longitudinal and time‐to‐event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469699/ https://www.ncbi.nlm.nih.gov/pubmed/35758865 http://dx.doi.org/10.1002/psp4.12835 |
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