Assessment of Sodium MRI at 7 Tesla as Predictor of Therapy Response and Survival in Glioblastoma Patients

Daniel Paech; Sebastian Regnery; Tanja Platt; Nicolas G R Behl; Nina Weckesser; Paul Windisch; Katerina Deike-Hofmann; Wolfgang Wick; Martin Bendszus; Stefan Rieken; Laila König; Mark E Ladd; Heinz-Peter Schlemmer; Jürgen Debus; Sebastian Adeberg

doi:10.3389/fnins.2021.782516

Assessment of Sodium MRI at 7 Tesla as Predictor of Therapy Response and Survival in Glioblastoma Patients

Front Neurosci. 2021 Dec 1:15:782516. doi: 10.3389/fnins.2021.782516. eCollection 2021.

Authors

Daniel Paech¹, Sebastian Regnery^{2

3}, Tanja Platt⁴, Nicolas G R Behl^{4

5}, Nina Weckesser¹, Paul Windisch², Katerina Deike-Hofmann¹, Wolfgang Wick⁶, Martin Bendszus⁷, Stefan Rieken^{2

3}, Laila König^{2

3}, Mark E Ladd^{4

8}, Heinz-Peter Schlemmer¹, Jürgen Debus^{2

3}, Sebastian Adeberg^{2

3}

Affiliations

¹ Division of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
³ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴ Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Siemens Healthcare GmbH, Erlangen, Germany.
⁶ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
⁷ Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
⁸ Faculty of Physics and Astronomy and Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.

Abstract

The purpose of this work was to prospectively investigate sodium (²³Na) MRI at 7 Tesla (T) as predictor of therapy response and survival in patients with glioblastoma (GBM). Thus, 20 GBM patients underwent ²³Na MRI at 7T before, immediately after and 6 weeks after chemoradiotherapy (CRT). The median tissue sodium concentration (TSC) inside the whole tumor excluding necrosis was determined. Initial response to CRT was assessed employing the updated response assessment in neuro-oncology working group (RANO) criteria. Clinical parameters, baseline TSC and longitudinal TSC differences were compared between patients with initial progressive disease (PD) and patients with initial stable disease (SD) using Fisher's exact tests and Mann-Whitney-U-tests. Univariate proportional hazard models for progression free survival (PFS) and overall survival (OS) were calculated using clinical parameters and TSC metrics as predictor variables. The analyses demonstrated that TSC developed heterogeneously over all patients following CRT. None of the TSC metrics differed significantly between cases of initial SD and initial PD. Furthermore, TSC metrics did not yield a significant association with PFS or OS. Conversely, the initial response according to the RANO criteria could significantly predict PFS [univariate HR (95%CI) = 0.02 (0.0001-0.21), p < 0.001] and OS [univariate HR = 0.17 (0.04-0.65), p = 0.005]. In conclusion, TSC showed treatment-related changes in GBM following CRT, but did not significantly correlate with the initial response according to the RANO criteria, PFS or OS. In contrast, the initial response according to the RANO criteria was a significant predictor of PFS and OS. Future investigations need to elucidate the reasons for treatment-related changes in TSC and their clinical value for response prediction in glioblastoma patients receiving CRT.

Keywords: brain neoplasm/secondary cases; glioblastoma; magnetic resonance imaging; response assessment; sodium MRI; ultra-high field (7 tesla).