TY - JOUR
T1 - Pulsed low-dose irradiation of orthotopic glioblastoma multiforme (GBM) in a pre-clinical model
T2 - Effects on vascularization and tumor control
AU - Dilworth, Joshua T.
AU - Krueger, Sarah A.
AU - Dabjan, Mohamad
AU - Grills, Inga S.
AU - Torma, John
AU - Wilson, George D.
AU - Marples, Brian
N1 - Funding Information:
The authors thank Megan Sinka C.N.M.T. for technical support. The work was funded by the Department of Radiation Oncology, Beaumont Health Systems and the Beaumont Health Systems Research Institute .
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/7
Y1 - 2013/7
N2 - Background and purpose To compare dose-escalated pulsed low-dose radiation therapy (PLRT) and standard radiation therapy (SRT). Methods and materials Intracranial U87MG GBM tumors were established in nude mice. Animals received whole brain irradiation with daily 2-Gy fractions given continuously (SRT) or in ten 0.2-Gy pulses separated by 3-min intervals (PLRT). Tumor response was evaluated using weekly CT and [18F]-FDG-PET scans. Brain tissue was subjected to immunohistochemistry and cytokine bead array to assess tumor and normal tissue effects. Results Median survival for untreated animals was 18 (SE ± 0.5) days. A significant difference in median survival was seen between SRT (29 ± 1.8 days) and PLRT (34.2 ± 1.9 days). Compared to SRT, PLRT resulted in a 31% (p < 0.01), 38% (p < 0.01), and 53% (p = 0.01) reduction in normalized tumor volume and a 48% (p < 0.01), 51% (p < 0.01), and 70% (p < 0.01) reduction in tumor growth rate following the administration of 10 Gy, 20 Gy, and 30 Gy, respectively. Compared to untreated tumors, PLRT resulted in similar tumor vascular density, while SRT produced a 40% reduction in tumor vascular density (p = 0.05). Compared to SRT, PLRT was associated with a 28% reduction in degenerating neurons in the surrounding brain parenchyma (p = 0.05). Conclusions Compared to SRT, PLRT resulted in greater inhibition of tumor growth and improved survival, which may be attributable to preservation of vascular density.
AB - Background and purpose To compare dose-escalated pulsed low-dose radiation therapy (PLRT) and standard radiation therapy (SRT). Methods and materials Intracranial U87MG GBM tumors were established in nude mice. Animals received whole brain irradiation with daily 2-Gy fractions given continuously (SRT) or in ten 0.2-Gy pulses separated by 3-min intervals (PLRT). Tumor response was evaluated using weekly CT and [18F]-FDG-PET scans. Brain tissue was subjected to immunohistochemistry and cytokine bead array to assess tumor and normal tissue effects. Results Median survival for untreated animals was 18 (SE ± 0.5) days. A significant difference in median survival was seen between SRT (29 ± 1.8 days) and PLRT (34.2 ± 1.9 days). Compared to SRT, PLRT resulted in a 31% (p < 0.01), 38% (p < 0.01), and 53% (p = 0.01) reduction in normalized tumor volume and a 48% (p < 0.01), 51% (p < 0.01), and 70% (p < 0.01) reduction in tumor growth rate following the administration of 10 Gy, 20 Gy, and 30 Gy, respectively. Compared to untreated tumors, PLRT resulted in similar tumor vascular density, while SRT produced a 40% reduction in tumor vascular density (p = 0.05). Compared to SRT, PLRT was associated with a 28% reduction in degenerating neurons in the surrounding brain parenchyma (p = 0.05). Conclusions Compared to SRT, PLRT resulted in greater inhibition of tumor growth and improved survival, which may be attributable to preservation of vascular density.
KW - Animal model
KW - Glioblastoma multiforme
KW - Orthotopic
KW - PLRT
KW - Pulsed radiation
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U2 - 10.1016/j.radonc.2013.05.022
DO - 10.1016/j.radonc.2013.05.022
M3 - Article
C2 - 23791366
AN - SCOPUS:84883185720
VL - 108
SP - 149
EP - 154
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
SN - 0167-8140
IS - 1
ER -