Clinical and Translational Oncology

, Volume 19, Issue 1, pp 51–57 | Cite as

Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab

  • A. HilarioEmail author
  • J. M. Sepulveda
  • A. Hernandez-Lain
  • E. Salvador
  • L. Koren
  • R. Manneh
  • Y. Ruano
  • A. Perez-Nuñez
  • A. Lagares
  • A. Ramos
Research Article


Background and purpose

In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability. Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response. Our objectives were: (1) to evaluate whether changes in DSC perfusion MRI-derived leakage could predict survival in recurrent glioblastoma, and (2) to estimate whether leakage at baseline was related to treatment outcome.

Materials and methods

We retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated with bevacizumab as second line chemotherapy. Leakage at baseline and changes in maximum leakage between baseline and the first follow-up after treatment were selected for quantitative analysis. Survival univariate analysis was made constructing survival curves using Kaplan–Meier method and comparing subgroups by log rank probability test.


Leakage reduction at 8 weeks after initiation of bevacizumab treatment had a significant influence on overall survival (OS) and progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer for patients with leakage reduction at the first follow-up. Higher leakage at baseline was associated with leakage reduction after treatment. Odds ratio of treatment response was 9 for patients with maximum leakage at baseline >5.


Leakage decrease may predict OS and PFS in recurrent glioblastomas treated with bevacizumab. Leakage reduction postulates as a potential biomarker for treatment response evaluation. Leakage at baseline seems to predict response to treatment, but was not independently associated with survival.


Brain Perfusion Glioblastoma Leakage Bevacizumab 



Confidence interval


Cerebral blood volume


Dynamic contrast-enhanced


Dynamic susceptibility-weighted contrast-enhanced


Echo-planar images


Food drug administration


Interquartile range


Negative predictive value


Overall survival


Progression-free survival


Positive predictive value


Response assessment in neuro-oncology


Region of interest


Receiver operating characteristic


Standard deviation


Vascular endothelial growth factor



This study was partially supported by grants: (1) FIS-PI 13/01258 from the Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, and (2) GEINO 12 from the Spanish Group for Research in Neurooncology (GEINO) to Aurelio Hernandez-Lain.

Compliance with ethical standards

Informed consent

Informed consent was obtained from all individuals participants included in the study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

For this type of study, formal consent is not required.


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2016

Authors and Affiliations

  1. 1.Department of RadiologyHospital 12 de OctubreMadridSpain
  2. 2.Department of NeuropathologyHospital 12 de OctubreMadridSpain
  3. 3.Department of Medical OncologyHospital 12 de OctubreMadridSpain
  4. 4.Department of NeurosurgeryHospital 12 de OctubreMadridSpain

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