Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 10/2019

01-10-2019 | Glioblastoma | Research Article

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

Authors: 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-Laín

Published in: Clinical and Translational Oncology | Issue 10/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMed
2.
Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT. Angiogenesis in brain tumours. Nat Rev Neurosci. 2007;8:610–22.CrossRefPubMed
3.
Sathornsumetee S, Cao Y, Marcello JE, Herndon JE 2nd, McLendon RE, Desjardins A, et al. Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan. J Clin Oncol. 2008;26:271–8.CrossRefPubMedPubMedCentral
4.
Poulsen HS, Urup T, Michaelsen SR, Staberg M, Villingshøj M, Lassen U. The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients. Cancer Manag Res. 2014;6:373–87.CrossRefPubMedPubMedCentral
5.
Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733–40.CrossRefPubMed
6.
Chinot O, Wick W, Mason W, et al. Phase III trial of bevacizumab added to standard radiotherapy and temozolomide for newly diagnosed glioblastoma: mature progression-free survival and preliminary overall survival results in AVAGlio. Neuro-Oncology. 2012;14(Suppl 6):vi101–vi105.
7.
Gilbert MR, Dignam J, Won M, et al. RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). J Clin Oncol. 2013;31(Suppl):abstr 1.CrossRef
8.
Wick W, Brandes AA, Gorlia T, et al. EORTC 26101 phase III trial exploring the combination of bevacizumab and lomustine in patients with first progression of a glioblastoma. J Clin Oncol. 2001;34(suppl):abstr.
9.
Johnson DR, Leeper HE, Uhm JH. Glioblastoma survival in the United States improved after Food and Drug Administration approval of bevacizumab: a population-based analysis. Cancer. 2013;119:3489–95.CrossRefPubMed
10.
Pakalniskis MG, Wells WA, Schwab MC, Froehlich HM, Jiang S, Li Z, et al. Tumor angiogenesis change estimated by using diffuse optical spectroscopic tomography: demonstrated correlation in women undergoing neoadjuvant chemotherapy for invasive breast cancer? Radiology. 2011;259:365–74.CrossRefPubMedPubMedCentral
11.
Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res. 2004;64:2941–55.CrossRefPubMed
12.
Hilario A, Sepulveda JM, Hernandez-Lain A, Salvador E, Koren L, Manneh R, et al. Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab. Clin Transl Oncol. 2017;19:51–7.CrossRefPubMed
13.
Gerstner ER, Sorensen AG, Jain RK, Batchelor TT. Advances in neuroimaging techniques for the evaluation of tumor growth, vascular permeability, and angiogenesis in gliomas. Curr Opin Neurol. 2008;21:728–35.CrossRefPubMed
14.
Pechman KR, Donohoe DL, Bedekar DP, Kurpad SN, Schmainda KM. Evaluation of combined bevacizumab plus irinotecan therapy in brain tumors using magnetic resonance imaging measures of relative cerebral blood volume. Magn Reson Med. 2012;68:1266–72.CrossRefPubMed
15.
Hilario A, Ramos A, Perez-Nuñez A, Salvador E, Millan JM, Lagares A, et al. The added value of apparent diffusion coefficient to cerebral blood volume in the preoperative grading of diffuse gliomas. AJNR Am J Neuroradiol. 2012;33:701–7.CrossRefPubMed
16.
Sorensen AG, Emblem KE, Polaskova P, Jennings D, Kim H, Ancukiewicz M, et al. Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion. Cancer Res. 2012;72:402–7.CrossRefPubMed
17.
Hilario A, Sepulveda JM, Perez-Nuñez A, Salvador E, Millan JM, et al. A prognostic model based on preoperative MRI predicts overall survival in patients with diffuse gliomas. AJNR Am J Neuroradiol. 2014;35:1096–102.CrossRefPubMed
18.
Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 2000;1(60):5954–8.
19.
Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343:1350–4.CrossRefPubMed
20.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.CrossRefPubMed
21.
Yoshimoto K, Dang J, Zhu S, Nathanson D, Huang T, Dumont R, et al. Development of a real-time RT-PCR assay for detecting EGFRvIII in glioblastoma samples. Clin Cancer Res. 2008;14:488–93.CrossRefPubMed
22.
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963–72.CrossRefPubMed
23.
Baumgarten P, Blank AE, Franz K, Hattingen E, Dunst M, Zeiner P, et al. Differential expression of vascular endothelial growth factor A, its receptors VEGFR-1, -2, and -3 and co-receptors neuropilin-1 and -2 does not predict bevacizumab response in human astrocytomas. Neuro Oncol. 2016;18:173–83.CrossRefPubMed
24.
Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699–708.CrossRefPubMedPubMedCentral
25.
Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, et al. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer. 2009;101:1986–94.CrossRefPubMedPubMedCentral
26.
Chen C, Huang R, MacLean A, Muzikansky A, Mukundan S, Wen PY, et al. Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival. J Neurooncol. 2013;115:267–76.CrossRefPubMed
27.
Schmainda KM, Prah M, Connelly J, Rand SD, Hoffman RG, et al. Dynamic-susceptibility contrast agent MRI measures of relative cerebral blood volume predict response to bevacizumab in recurrent high-grade glioma. NeuroOncol. 2014;16:880–8.
28.
Kickingereder P, Wiestler B, Burth S, Wick A, Nowosielski M, et al. Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma. Neuro Oncol. 2015;17:1139–47.CrossRefPubMedPubMedCentral
29.
Harris RJ, Cloughesy TF, Hardy AJ, Liau LM, Pope WB, Nghiemphu PL, et al. MRI perfusion measurements calculated using advanced deconvolution techniques predict survival in recurrent glioblastoma treated with bevacizumab. J Neurooncol. 2015;122:497–505.CrossRefPubMed
30.
Tamura R, Tanaka T, Miyake K, Tabei Y, Ohara K, Sampetrean O, et al. Histopathological investigation of glioblastomas resected under bevacizumab treatment. Oncotarget. 2016;7:52423–355.PubMedPubMedCentral
31.
D'Alessandris QG, Martini M, Cenci T, Capo G, Ricci-Vitiani L, Larocca LM, et al. VEGF isoforms as outcome biomarker for anti-angiogenic therapy in recurrent glioblastoma. Neurology. 2015;84:1906–8.CrossRefPubMed
32.
Martini M, de Pascalis I, D'Alessandris QG, Fiorentino V, Pierconti F, Marei HE, et al. VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma. BMC Cancer. 2018;18:553.CrossRefPubMedPubMedCentral
33.
Molina D, Pérez-Beteta J, Martínez-González A, Sepúlveda JM, Peralta S, Gil-Gil MJ, et al. Geometrical measures obtained from pretreatment postcontrast T1 weighted MRIs predict survival benefits from bevacizumab in glioblastoma patients. PLoS ONE. 2016;11(8):e0161484.CrossRefPubMedPubMedCentral
34.
Grossmann P, Narayan V, Chang K, Rahman R, Abrey L, Reardon DA, et al. Quantitative imaging biomarkers for risk stratification of patients with recurrent glioblastoma treated with bevacizumab. Neuro Oncol. 2017;19:1688–97.CrossRefPubMedPubMedCentral
35.
Chang K, Zhang B, Guo X, Zong M, Rahman R, Sanchez D, et al. Multimodal imaging patterns predict survival in recurrent glioblastoma patients treated with bevacizumab. Neuro Oncol. 2016;18:1680–7.CrossRefPubMedPubMedCentral
Metadata
Title
Correlation of radiological and immunochemical parameters with clinical outcome in patients with recurrent glioblastoma treated with Bevacizumab
Authors
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-Laín
Publication date
01-10-2019
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 10/2019
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02070-6

Other articles of this Issue 10/2019

Clinical and Translational Oncology 10/2019 Go to the issue

Research Article

The detection and clinical significance of peripheral regulatory CD4+CD25hiCD127low T cells in patients with non-small cell lung cancer

Research article

Seven genes for the prognostic prediction in patients with glioma

Research Article

Added value of diffusion-weighted MRI for nodal radiotherapy planning in pelvic malignancies

Research Article

Comparison of overall survival and quality of life between patients undergoing anal reconstruction and patients undergoing traditional lower abdominal stoma after radical resection

Brief Research Article

ΔNp73 status in peritoneal and ovarian dissemination of appendicular adenocarcinoids (goblet cells)

Research Article

Data from real world to evaluate the efficacy of osimertinib in non-small cell lung cancer patients with central nervous system metastasis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits