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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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Detalles Bibliográficos
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
Descripción
Sumario: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.