Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.
Author: García Romero, Noemí; Palacín Aliana, I.; Madurga Lacalle, Rodrigo; Carrión Navarro, Josefa; Esteban Rubio, S.; Jiménez, B.; Collazo, A.; Pérez Rodríguez, F.; Ortiz de Mendivil, A.; Fernández Carballal, C.; García Duque, s.; Diamantopoulos-Fernández, J.; Belda Iniesta, C.; Prat Acín, R.; Sánchez Gómez, P.; Calvo, E.; Ayuso Sacido, Ángel
Abstract: Background Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. Methods We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. Results We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. Conclusions Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.
Universal identifier: http://hdl.handle.net/10641/2022
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