Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma
Noemí Garcia‐Romero, Irina Palacín-Aliana, Rodrigo Madurga, Josefa Carrión-Navarro, Susana Esteban-Rubio, Beatriz Jiménez, Ana Collazo, Francisco José Pérez‐Rodríguez, Ana Ortiz de Méndivil, C. Fernández-Carballal, Sara García-Duque, Jorge Diamantopoulos Fernández, Cristóbal Belda-Iniesta, Ricardo Prat-Acín, Pilar Sánchez‐Gómez, Emiliano Calvo, Ángel Ayuso‐Sacido
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.