BMC Medicine (Jun 2020)

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma

  • N. García-Romero,
  • I. Palacín-Aliana,
  • R. Madurga,
  • J. Carrión-Navarro,
  • S. Esteban-Rubio,
  • B. Jiménez,
  • A. Collazo,
  • F. Pérez-Rodríguez,
  • A. Ortiz de Mendivil,
  • C. Fernández-Carballal,
  • S. García-Duque,
  • J. Diamantopoulos-Fernández,
  • C. Belda-Iniesta,
  • R. Prat-Acín,
  • P. Sánchez-Gómez,
  • E. Calvo,
  • A. Ayuso-Sacido

DOI
https://doi.org/10.1186/s12916-020-01610-0
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 16

Abstract

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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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