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 [(18)F]-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±1.8days) and PLRT (34.2±1.9days). 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 10Gy, 20Gy, and 30Gy, 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.
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 [(18)F]-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±1.8days) and PLRT (34.2±1.9days). 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 10Gy, 20Gy, and 30Gy, 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.
Authors: Stefanie Kirschner; Manuela C Felix; Linda Hartmann; Miriam Bierbaum; Máté E Maros; Hans U Kerl; Frederik Wenz; Gerhard Glatting; Martin Kramer; Frank A Giordano; Marc A Brockmann Journal: J Neurooncol Date: 2015-01-22 Impact factor: 4.130
Authors: Muayad F Almahariq; Thomas J Quinn; Jessica D Arden; P T Roskos; George D Wilson; Brian Marples; Inga S Grills; Peter Y Chen; Daniel J Krauss; Prakash Chinnaiyan; Joshua T Dilworth Journal: Neuro Oncol Date: 2021-03-25 Impact factor: 12.300
Authors: Stefanie Kirschner; Bettina Mürle; Manuela Felix; Anna Arns; Christoph Groden; Frederik Wenz; Andreas Hug; Gerhard Glatting; Martin Kramer; Frank A Giordano; Marc A Brockmann Journal: PLoS One Date: 2016-11-09 Impact factor: 3.240