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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

Abstract

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.

Results

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.

Conclusions

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.

Keywords

Brain Perfusion Glioblastoma Leakage Bevacizumab 

Abbreviations

CI

Confidence interval

CBV

Cerebral blood volume

DCE

Dynamic contrast-enhanced

DSC

Dynamic susceptibility-weighted contrast-enhanced

EPI

Echo-planar images

FDA

Food drug administration

IQR

Interquartile range

NPV

Negative predictive value

OS

Overall survival

PFS

Progression-free survival

PPV

Positive predictive value

RANO

Response assessment in neuro-oncology

ROI

Region of interest

ROC

Receiver operating characteristic

SD

Standard deviation

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

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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