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Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors

Three‐dimensional and density‐based tumor metrics have been suggested to better discriminate tumor response to treatment than unidimensional metrics, particularly for tumors exhibiting nonuniform size changes. In the developed pharmacometric modeling framework based on data from 77 imatinib‐treated...

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Autores principales: Schindler, E, Krishnan, SM, Mathijssen, RHJ, Ruggiero, A, Schiavon, G, Friberg, LE
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529749/
https://www.ncbi.nlm.nih.gov/pubmed/28379635
http://dx.doi.org/10.1002/psp4.12195
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author Schindler, E
Krishnan, SM
Mathijssen, RHJ
Ruggiero, A
Schiavon, G
Friberg, LE
author_facet Schindler, E
Krishnan, SM
Mathijssen, RHJ
Ruggiero, A
Schiavon, G
Friberg, LE
author_sort Schindler, E
collection PubMed
description Three‐dimensional and density‐based tumor metrics have been suggested to better discriminate tumor response to treatment than unidimensional metrics, particularly for tumors exhibiting nonuniform size changes. In the developed pharmacometric modeling framework based on data from 77 imatinib‐treated gastrointestinal patients, the time‐courses of liver metastases' maximum transaxial diameters, software‐calculated actual volumes (V(actual)) and calculated ellipsoidal volumes were characterized by logistic growth models, in which imatinib induced a linear dose‐dependent size reduction. An indirect response model best described the reduction in density. Substantial interindividual variability in the drug effect of all response assessments and additional interlesion variability in the drug effect on density were identified. The predictive ability of longitudinal tumor unidimensional and three‐dimensional size and density on overall survival (OS) and progression‐free survival (PFS) were compared using parametric time‐to‐event models. Death hazard increased with increasing V(actual). This framework may guide early clinical interventions based on three‐dimensional tumor responses to enhance benefits for patients with gastrointestinal stromal tumors (GIST).
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spelling pubmed-55297492017-08-02 Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors Schindler, E Krishnan, SM Mathijssen, RHJ Ruggiero, A Schiavon, G Friberg, LE CPT Pharmacometrics Syst Pharmacol Original Articles Three‐dimensional and density‐based tumor metrics have been suggested to better discriminate tumor response to treatment than unidimensional metrics, particularly for tumors exhibiting nonuniform size changes. In the developed pharmacometric modeling framework based on data from 77 imatinib‐treated gastrointestinal patients, the time‐courses of liver metastases' maximum transaxial diameters, software‐calculated actual volumes (V(actual)) and calculated ellipsoidal volumes were characterized by logistic growth models, in which imatinib induced a linear dose‐dependent size reduction. An indirect response model best described the reduction in density. Substantial interindividual variability in the drug effect of all response assessments and additional interlesion variability in the drug effect on density were identified. The predictive ability of longitudinal tumor unidimensional and three‐dimensional size and density on overall survival (OS) and progression‐free survival (PFS) were compared using parametric time‐to‐event models. Death hazard increased with increasing V(actual). This framework may guide early clinical interventions based on three‐dimensional tumor responses to enhance benefits for patients with gastrointestinal stromal tumors (GIST). John Wiley and Sons Inc. 2017-05-30 2017-07 /pmc/articles/PMC5529749/ /pubmed/28379635 http://dx.doi.org/10.1002/psp4.12195 Text en © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Schindler, E
Krishnan, SM
Mathijssen, RHJ
Ruggiero, A
Schiavon, G
Friberg, LE
Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors
title Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors
title_full Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors
title_fullStr Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors
title_full_unstemmed Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors
title_short Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors
title_sort pharmacometric modeling of liver metastases' diameter, volume, and density and their relation to clinical outcome in imatinib‐treated patients with gastrointestinal stromal tumors
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529749/
https://www.ncbi.nlm.nih.gov/pubmed/28379635
http://dx.doi.org/10.1002/psp4.12195
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