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Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies

BACKGROUND: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed...

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Autores principales: Singleton, Kyle W, Porter, Alyx B, Hu, Leland S, Johnston, Sandra K, Bond, Kamila M, Rickertsen, Cassandra R, De Leon, Gustavo, Whitmire, Scott A, Clark-Swanson, Kamala R, Mrugala, Maciej M, Swanson, Kristin R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447137/
https://www.ncbi.nlm.nih.gov/pubmed/32864609
http://dx.doi.org/10.1093/noajnl/vdaa085
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author Singleton, Kyle W
Porter, Alyx B
Hu, Leland S
Johnston, Sandra K
Bond, Kamila M
Rickertsen, Cassandra R
De Leon, Gustavo
Whitmire, Scott A
Clark-Swanson, Kamala R
Mrugala, Maciej M
Swanson, Kristin R
author_facet Singleton, Kyle W
Porter, Alyx B
Hu, Leland S
Johnston, Sandra K
Bond, Kamila M
Rickertsen, Cassandra R
De Leon, Gustavo
Whitmire, Scott A
Clark-Swanson, Kamala R
Mrugala, Maciej M
Swanson, Kristin R
author_sort Singleton, Kyle W
collection PubMed
description BACKGROUND: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. METHODS: DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. RESULTS: In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. CONCLUSION: DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.
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spelling pubmed-74471372020-08-27 Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies Singleton, Kyle W Porter, Alyx B Hu, Leland S Johnston, Sandra K Bond, Kamila M Rickertsen, Cassandra R De Leon, Gustavo Whitmire, Scott A Clark-Swanson, Kamala R Mrugala, Maciej M Swanson, Kristin R Neurooncol Adv Basic and Translational Investigations BACKGROUND: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. METHODS: DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. RESULTS: In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. CONCLUSION: DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes. Oxford University Press 2020-07-09 /pmc/articles/PMC7447137/ /pubmed/32864609 http://dx.doi.org/10.1093/noajnl/vdaa085 Text en © The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic and Translational Investigations
Singleton, Kyle W
Porter, Alyx B
Hu, Leland S
Johnston, Sandra K
Bond, Kamila M
Rickertsen, Cassandra R
De Leon, Gustavo
Whitmire, Scott A
Clark-Swanson, Kamala R
Mrugala, Maciej M
Swanson, Kristin R
Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
title Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
title_full Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
title_fullStr Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
title_full_unstemmed Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
title_short Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
title_sort days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
topic Basic and Translational Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447137/
https://www.ncbi.nlm.nih.gov/pubmed/32864609
http://dx.doi.org/10.1093/noajnl/vdaa085
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