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.
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