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Correlation of radiological and immunochemical parameters with clinical outcome in patients with recurrent glioblastoma treated with Bevacizumab

  • R. A. Manneh Kopp
  • J. M. Sepúlveda-Sánchez
  • Y. Ruano
  • O. Toldos
  • A. Pérez Núñez
  • D. Cantero
  • A. Hilario
  • A. Ramos
  • G. de Velasco
  • P. Sánchez-Gómez
  • A. Hernández-LaínEmail author
Research Article

Abstract

Background

Some phase 2 trials had reported encouraging progression-free survival with Bevacizumab in monotherapy or combined with chemotherapy in glioblastoma. However, phase 3 trials showed a significant improvement in progression free survival without a benefit in overall survival. To date, there are no predictive biomarker of response for Bevacizumab in glioblastoma.

Methods

We used Immunochemical analysis on tumor samples and pretreatment and post-treatment perfusion-MRI to try to identify possible predictive angiogenesis-related biomarkers of response and survival in patients with glioblastoma treated with bevacizumab in the first recurrence. We analyzed histological parameters: vascular proliferation, mitotic number and Ki-67 index; molecular factors: MGMT promoter methylation, EGFR amplification and EGFR variant III; immunohistochemical: MET, Midkine, HIF1, VEGFA, VEGF-R2, CD44, Olig2, microvascular area and microvascular density; and radiological: rCBV.

Results

In the statistical analysis, no significant correlation of any histological, molecular, microvascular or radiological parameters could be demonstrated with the response rate, PFS or OS with bevacizumab treatment.

Conclusion

Unfortunately, in this histopathological, molecular, immunohistochemical and neuroradiological study we did not find any predictive biomarker of response or survival benefit for Bevacizumab in glioblastoma.

Keywords

Bevacizumab Glioblastoma Biomarkers Microvacular density Microvascular area 

Notes

Author contributions

Dr. RAMK project conception, project organization, project execution and writing first draft. Dr. JMS project conception, project organization, project execution, manuscript review and critique. Dr. YR project execution. Dr. OT project execution. Dr. AP: project conception, manuscript review and critique. DC project execution. Dr. AH: project conception, imaging, manuscript review. Dr. AR: project execution, imaging. Dr. VOR project execution. Dr. PS project conception, project organization, project execution, manuscript review and critique. Dr. AH project conception, project organization, project execution, manuscript review and critique.

Funding

This work was supported by a grant from the GEINO (Spanish Group for Research in Neurooncology) and a Grant number PI/13/01258 from ISCIII and co-funded with the European Regional Development Funds.

Compliance with ethical standards

Conflict of interest

Dr. Manneh Kopp reports no disclosures. Dr. Sepúlveda-Sánchez reports no disclosures. Dr. Ruano reports no disclosures. Dr. Toldos reports no disclosures. Dr. Perez-Nuñez reports no disclosures. Diana Cantero reports no disclosures. Dr. Hilario reports no disclosures. Dr. Ramos reports no disclosures. Dr. Velasco Oria de Rueda reports no disclosures. Dr. Sánchez-Gómez reports no disclosures. Dr. Hernandez-Lain reports no disclosures.

Supplementary material

12094_2019_2070_MOESM1_ESM.ppt (1.8 mb)
Supplementary figure 1. FISH Analysis of EGFR. FISH assay with locus-specific probes for EGFR paired with centromere probes for chromosomes 7 (CEP7) (Vysis, Downers Grove, IL, USA). Signals were scored in at least 200 intact nuclei. EGFR amplification was considered when more than 10% of tumor cells exhibited a EGFR:CEP7 ratio ≥ 2.0 Supplementary figure 2: OS and PFS for BVZ Kaplan Meier Illustrates the median OS (A) and median PFS (B) curves of the entire cohort for BVZ (PPT 1893 kb)

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  • R. A. Manneh Kopp
    • 1
  • J. M. Sepúlveda-Sánchez
    • 1
    • 6
  • Y. Ruano
    • 2
  • O. Toldos
    • 2
  • A. Pérez Núñez
    • 3
  • D. Cantero
    • 2
  • A. Hilario
    • 4
  • A. Ramos
    • 4
  • G. de Velasco
    • 1
  • P. Sánchez-Gómez
    • 5
  • A. Hernández-Laín
    • 2
    • 6
    Email author
  1. 1.Medical OncologyHospital Universitario 12 de OctubreMadridSpain
  2. 2.Department of Pathology (Neuropathology)Hospital Universitario 12 de OctubreMadridSpain
  3. 3.Department of NeurosurgeryHospital Universitario 12 de OctubreMadridSpain
  4. 4.Departments Radiology (A.H., A.R.)Hospital Universitario 12 de OctubreMadridSpain
  5. 5.Neuro-Oncology UnitHealth Institute Carlos III-UFIECMadridSpain
  6. 6.Instituto de Investigación Hospital 12 de Octubre (i+12)MadridSpain

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