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Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide

Glioblastoma multiforme (GBM) is a common and aggressive malignant brain cancer with a mean survival time of approximately 15 months after initial diagnosis. Currently, the standard-of-care (SOC) treatment for this disease consists of radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ...

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Autores principales: Mowday, Alexandra M., Lieuwes, Natasja G., Biemans, Rianne, Marcus, Damiënne, Rezaeifar, Behzad, Reniers, Brigitte, Verhaegen, Frank, Theys, Jan, Dubois, Ludwig J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352586/
https://www.ncbi.nlm.nih.gov/pubmed/32549357
http://dx.doi.org/10.3390/cancers12061585
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author Mowday, Alexandra M.
Lieuwes, Natasja G.
Biemans, Rianne
Marcus, Damiënne
Rezaeifar, Behzad
Reniers, Brigitte
Verhaegen, Frank
Theys, Jan
Dubois, Ludwig J.
author_facet Mowday, Alexandra M.
Lieuwes, Natasja G.
Biemans, Rianne
Marcus, Damiënne
Rezaeifar, Behzad
Reniers, Brigitte
Verhaegen, Frank
Theys, Jan
Dubois, Ludwig J.
author_sort Mowday, Alexandra M.
collection PubMed
description Glioblastoma multiforme (GBM) is a common and aggressive malignant brain cancer with a mean survival time of approximately 15 months after initial diagnosis. Currently, the standard-of-care (SOC) treatment for this disease consists of radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ). We sought to develop an orthotopic preclinical model of GBM and to optimize a protocol for non-invasive monitoring of tumor growth, allowing for determination of the efficacy of SOC therapy using a targeted RT strategy combined with TMZ. A strong correlation (r = 0.80) was observed between contrast-enhanced (CE)-CT-based volume quantification and bioluminescent (BLI)-integrated image intensity when monitoring tumor growth, allowing for BLI imaging as a substitute for CE-CT. An optimized parallel-opposed single-angle RT beam plan delivered on average 96% of the expected RT dose (20, 30 or 60 Gy) to the tumor. Normal tissue on the ipsilateral and contralateral sides of the brain were spared 84% and 99% of the expected dose, respectively. An increase in median survival time was demonstrated for all SOC regimens compared to untreated controls (average 5.2 days, p < 0.05), but treatment was not curative, suggesting the need for novel treatment options to increase therapeutic efficacy.
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spelling pubmed-73525862020-07-15 Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide Mowday, Alexandra M. Lieuwes, Natasja G. Biemans, Rianne Marcus, Damiënne Rezaeifar, Behzad Reniers, Brigitte Verhaegen, Frank Theys, Jan Dubois, Ludwig J. Cancers (Basel) Article Glioblastoma multiforme (GBM) is a common and aggressive malignant brain cancer with a mean survival time of approximately 15 months after initial diagnosis. Currently, the standard-of-care (SOC) treatment for this disease consists of radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ). We sought to develop an orthotopic preclinical model of GBM and to optimize a protocol for non-invasive monitoring of tumor growth, allowing for determination of the efficacy of SOC therapy using a targeted RT strategy combined with TMZ. A strong correlation (r = 0.80) was observed between contrast-enhanced (CE)-CT-based volume quantification and bioluminescent (BLI)-integrated image intensity when monitoring tumor growth, allowing for BLI imaging as a substitute for CE-CT. An optimized parallel-opposed single-angle RT beam plan delivered on average 96% of the expected RT dose (20, 30 or 60 Gy) to the tumor. Normal tissue on the ipsilateral and contralateral sides of the brain were spared 84% and 99% of the expected dose, respectively. An increase in median survival time was demonstrated for all SOC regimens compared to untreated controls (average 5.2 days, p < 0.05), but treatment was not curative, suggesting the need for novel treatment options to increase therapeutic efficacy. MDPI 2020-06-15 /pmc/articles/PMC7352586/ /pubmed/32549357 http://dx.doi.org/10.3390/cancers12061585 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mowday, Alexandra M.
Lieuwes, Natasja G.
Biemans, Rianne
Marcus, Damiënne
Rezaeifar, Behzad
Reniers, Brigitte
Verhaegen, Frank
Theys, Jan
Dubois, Ludwig J.
Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
title Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
title_full Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
title_fullStr Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
title_full_unstemmed Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
title_short Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
title_sort use of a luciferase-expressing orthotopic rat brain tumor model to optimize a targeted irradiation strategy for efficacy testing with temozolomide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352586/
https://www.ncbi.nlm.nih.gov/pubmed/32549357
http://dx.doi.org/10.3390/cancers12061585
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