Myoinositol as a biomarker in recurrent glioblastoma treated with bevacizumab : a 1H-magnetic resonance spectroscopy study

  • Background: Antiangiogenic treatment of glioblastomas with Bevacizumab lacks predictive markers. Myoinositol (MI) is an organic osmolyte, with intracellular concentration changes depending on the extracellular osmolality. Since Bevacizumab markedly reduces tumor edema and influences the tumor microenvironment, we investigated whether the MI concentration in the tumor changes during therapy. Methods: We used 1H-magnetic resonance spectroscopy to measure the MI concentrations in the tumor and contralateral control tissue of 39 prospectively recruited patients with recurrent glioblastomas before and 8–12 weeks after starting therapy. 30 patients received Bevacizumab and 9 patients were treated with CCNU/VM26 as control. We performed a survival analysis to evaluate MI as a predictive biomarker for Bevacizumab therapy. Results: MI concentrations increased significantly during Bevacizumab therapy in tumor (p < .001) and control tissue (p = .001), but not during CCNU/VM26 treatment. For the Bevacizumab cohort, higher MI concentrations in the control tissue at baseline (p = .021) and higher differences between control and tumor tissue (delta MI, p = .011) were associated with longer survival. A Kaplan-Meier analysis showed a median OS of 164 days for patients with a deltaMI < 1,817 mmol/l and 275 days for patients with a deltaMI > 1,817 mmol/l. No differences were observed for the relative changes or the post treatment concentrations. Additionally calculated creatine concentrations showed no differences in between subgroups or between pre and post treatment measurements. Conclusion: Our data suggest that recurrent glioblastoma shows a strong metabolic reaction to Bevacizumab. Further, our results support the hypothesis that MI might be a marker for early tumor cell invasion. Pre-therapeutic MI concentrations are predictive of overall survival in patients with recurrent glioblastoma treated with Bevacizumab.
Metadaten
Author:Eike SteidlORCiDGND, Ulrich Pilatus, Elke HattingenORCiDGND, Joachim Peter SteinbachORCiDGND, Friedhelm Zanella, Michael Wilfried RonellenfitschORCiDGND, Oliver Bähr
URN:urn:nbn:de:hebis:30:3-420028
DOI:https://doi.org/10.1371/journal.pone.0168113
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28033329
Parent Title (English):PLoS one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Contributor(s):Han-Chiao Isaac Chen
Document Type:Article
Language:English
Date of Publication (online):2017/01/12
Date of first Publication:2016/12/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/01/12
Volume:11
Issue:(12): e0168113
Page Number:15
First Page:1
Last Page:15
Note:
Copyright: © 2016 Steidl et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS-PPN:415174171
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0