Skip to main content
Top
Published in: Clinical and Translational Oncology 1/2017

01-01-2017 | Research Article

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

Authors: A. Hilario, J. M. Sepulveda, A. Hernandez-Lain, E. Salvador, L. Koren, R. Manneh, Y. Ruano, A. Perez-Nuñez, A. Lagares, A. Ramos

Published in: Clinical and Translational Oncology | Issue 1/2017

Login to get access

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.
Literature
1.
go back to reference Narita Y. Drug review: safety and efficacy of bevacizumab for glioblastoma and other brain tumors. Jpn J Clin Oncol. 2013;43(6):587–95.CrossRefPubMed Narita Y. Drug review: safety and efficacy of bevacizumab for glioblastoma and other brain tumors. Jpn J Clin Oncol. 2013;43(6):587–95.CrossRefPubMed
2.
go back to reference Sweet JA, Feinberg ML, Sherman JH. The role of avastin in the management of recurrent glioblastoma. Neurosurg Clin N Am. 2012;23:331–41.CrossRefPubMed Sweet JA, Feinberg ML, Sherman JH. The role of avastin in the management of recurrent glioblastoma. Neurosurg Clin N Am. 2012;23:331–41.CrossRefPubMed
3.
go back to reference Thomas AA, Omuro A. Current role of antiangiogenic strategies for glioblastoma. Curr Treat Options Oncol. 2014;15:551–66.CrossRefPubMed Thomas AA, Omuro A. Current role of antiangiogenic strategies for glioblastoma. Curr Treat Options Oncol. 2014;15:551–66.CrossRefPubMed
4.
go back to reference Pope WB, Lai A, Mehta R, Kim HJ, Qiao J, Xue X, et al. Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma. AJNR Am J Neuroradiol. 2011;32:882–9.CrossRefPubMed Pope WB, Lai A, Mehta R, Kim HJ, Qiao J, Xue X, et al. Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma. AJNR Am J Neuroradiol. 2011;32:882–9.CrossRefPubMed
5.
go back to reference Jeon JY, Kovanlikaya I, Boockvar JA, Mao X, Shin B, Burkhardt J, et al. Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study. AJNR Am J Neuroradiol. 2012;33:2095–102.CrossRefPubMed Jeon JY, Kovanlikaya I, Boockvar JA, Mao X, Shin B, Burkhardt J, et al. Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study. AJNR Am J Neuroradiol. 2012;33:2095–102.CrossRefPubMed
6.
go back to reference Kickingereder P, Wiestler B, Graf M, Heiland S, Schlemmer HP, Wick W, et al. Evaluation of dynamic contrast-enhanced MRI derived microvascular permeability in recurrent glioblastoma treated with bevacizumab. J Neurooncol. 2015;121:373–80.CrossRefPubMed Kickingereder P, Wiestler B, Graf M, Heiland S, Schlemmer HP, Wick W, et al. Evaluation of dynamic contrast-enhanced MRI derived microvascular permeability in recurrent glioblastoma treated with bevacizumab. J Neurooncol. 2015;121:373–80.CrossRefPubMed
7.
go back to reference 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 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
9.
go back to reference 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 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
10.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fischer B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolamide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fischer B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolamide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMed
11.
go back to reference Lacerda S, Law M. Magnetic resonance perfusion and permeability imaging in brain tumors. Neuroimaging Clin N Am. 2009;19:527–57.CrossRefPubMed Lacerda S, Law M. Magnetic resonance perfusion and permeability imaging in brain tumors. Neuroimaging Clin N Am. 2009;19:527–57.CrossRefPubMed
12.
go back to reference Mouridsen K, Christensen S, Gyldensted L, Ostergaard L. Automatic selection of arterial input function using cluster analysis. Magn Reson Med. 2006;55:524–31.CrossRefPubMed Mouridsen K, Christensen S, Gyldensted L, Ostergaard L. Automatic selection of arterial input function using cluster analysis. Magn Reson Med. 2006;55:524–31.CrossRefPubMed
13.
go back to reference Wu O, Østergaard L, Weisskoff RM, Benner T, Rosen BR, Sorensen AG. Tracer arrival timing-insensitive technique for estimating flow in MR perfusión-weighted imaging using singular value decomposition with a block-circulant deconvolution matrix. Magn Reson Med. 2003;50(1):164–74.CrossRefPubMed Wu O, Østergaard L, Weisskoff RM, Benner T, Rosen BR, Sorensen AG. Tracer arrival timing-insensitive technique for estimating flow in MR perfusión-weighted imaging using singular value decomposition with a block-circulant deconvolution matrix. Magn Reson Med. 2003;50(1):164–74.CrossRefPubMed
14.
go back to reference Bouterllier T, Kudo K, Pautot F, Sasaki M. Bayesian hemodynamic parameter estimation by bolus tracking perfusión weighted imaging. IEEE Trans Med Imaging. 2012;31(7):1381–95.CrossRef Bouterllier T, Kudo K, Pautot F, Sasaki M. Bayesian hemodynamic parameter estimation by bolus tracking perfusión weighted imaging. IEEE Trans Med Imaging. 2012;31(7):1381–95.CrossRef
16.
go back to reference Cohen MH, Shen YL, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009;14:1131–8.CrossRefPubMed Cohen MH, Shen YL, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009;14:1131–8.CrossRefPubMed
17.
go back to reference 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 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
18.
go back to reference Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, et al. Phase II trial of single agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740–5.CrossRefPubMed Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, et al. Phase II trial of single agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740–5.CrossRefPubMed
19.
go back to reference Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolamide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709–22.CrossRefPubMed Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolamide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709–22.CrossRefPubMed
20.
go back to reference 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 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
21.
go back to reference Fischer I, Cunliffe CH, Bollo RJ, Raza S, Monoky D, Chiriboga L, et al. High-grade glioma before and after treatment with radiation and Avastin: initial observations. J Neurooncol. 2008;10:700–8. Fischer I, Cunliffe CH, Bollo RJ, Raza S, Monoky D, Chiriboga L, et al. High-grade glioma before and after treatment with radiation and Avastin: initial observations. J Neurooncol. 2008;10:700–8.
22.
go back to reference Wagle N, Nghiemphu L, Lai A, Pope W, Mischel PS, Cloughesy T. Update and developments in the treatment of glioblastoma multiforme—focus on bevacizumab. Pharmacogenomics Pers Med. 2010;3:79–85. Wagle N, Nghiemphu L, Lai A, Pope W, Mischel PS, Cloughesy T. Update and developments in the treatment of glioblastoma multiforme—focus on bevacizumab. Pharmacogenomics Pers Med. 2010;3:79–85.
23.
go back to reference Pope WB, Lai A, Nghiemphu P, Mischel P, Cloughesy TF. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology. 2006;66:1258–60.CrossRefPubMed Pope WB, Lai A, Nghiemphu P, Mischel P, Cloughesy TF. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology. 2006;66:1258–60.CrossRefPubMed
24.
go back to reference de Groot JF, Yung WKA. Bevacizumab and irinotecan in the treatments of recurrent malignant gliombas. Cancer J. 2008;14:279–85.CrossRefPubMed de Groot JF, Yung WKA. Bevacizumab and irinotecan in the treatments of recurrent malignant gliombas. Cancer J. 2008;14:279–85.CrossRefPubMed
25.
go back to reference Moen M. Bevacizumab: in previously treated glioblastoma. Drugs. 2010;62(3):297–303. Moen M. Bevacizumab: in previously treated glioblastoma. Drugs. 2010;62(3):297–303.
26.
go back to reference Chung C, Jalali S, Foltz W, Burrell K, Wildgoose P, Lindsay P, et al. Imaging biomarker dynamics in an intracranial murine glioma study of radiation and antiangiogenic therapy. Int J Radiation Oncol Biol Phys. 2013;85(3):805–12.CrossRef Chung C, Jalali S, Foltz W, Burrell K, Wildgoose P, Lindsay P, et al. Imaging biomarker dynamics in an intracranial murine glioma study of radiation and antiangiogenic therapy. Int J Radiation Oncol Biol Phys. 2013;85(3):805–12.CrossRef
27.
go back to reference Zhang W, Kreisl T, Solomon J. Acute effects of bevacizumab on glioblastoma vascularity assessed with DCE-MRI and relation to patient survival. Proc Intl Soc Magn Reson Med. 2009;17(30):5125. Zhang W, Kreisl T, Solomon J. Acute effects of bevacizumab on glioblastoma vascularity assessed with DCE-MRI and relation to patient survival. Proc Intl Soc Magn Reson Med. 2009;17(30):5125.
28.
go back to reference Verhoeff JJ, Lavini C, van Linde ME, Stalpers LJ, Majoie CB, Reijneveld JC, et al. Bevacizumab and dose-intense temozolamide in recurrent high-grade glioma. Ann Oncol. 2010;21:1723–7.CrossRefPubMed Verhoeff JJ, Lavini C, van Linde ME, Stalpers LJ, Majoie CB, Reijneveld JC, et al. Bevacizumab and dose-intense temozolamide in recurrent high-grade glioma. Ann Oncol. 2010;21:1723–7.CrossRefPubMed
29.
go back to reference Sorensen AG, Batchelor TT, Zhang WT, Cheng PJ, Yeo P, Wang M, et al. A “vascular normalization index” as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res. 2009;69:5296–300.CrossRefPubMedPubMedCentral Sorensen AG, Batchelor TT, Zhang WT, Cheng PJ, Yeo P, Wang M, et al. A “vascular normalization index” as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res. 2009;69:5296–300.CrossRefPubMedPubMedCentral
Metadata
Title
Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab
Authors
A. Hilario
J. M. Sepulveda
A. Hernandez-Lain
E. Salvador
L. Koren
R. Manneh
Y. Ruano
A. Perez-Nuñez
A. Lagares
A. Ramos
Publication date
01-01-2017
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 1/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-016-1502-4

Other articles of this Issue 1/2017

Clinical and Translational Oncology 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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