PURPOSE: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. METHODS AND MATERIALS: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1(nu) mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as a single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. RESULTS: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. CONCLUSIONS: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.
PURPOSE: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. METHODS AND MATERIALS: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1(nu) mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as a single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. RESULTS: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. CONCLUSIONS: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.
Authors: Julie Bolcaen; Benedicte Descamps; Karel Deblaere; Tom Boterberg; Giorgio Hallaert; Caroline Van den Broecke; Elke Decrock; Anne Vral; Luc Leybaert; Christian Vanhove; Ingeborg Goethals Journal: J Neurooncol Date: 2014-07-29 Impact factor: 4.130
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: 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