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

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

doi:10.3389/fnins.2021.782516

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.

Highlights

The overall prognosis of glioblastoma (GBM) remains poor despite gross tumor resection followed by chemoradiotherapy (CRT), but long-term survival can be achieved in a small subgroup of patients (Stupp et al, 2005, 2009)
According to the response assessment in neuro-oncology working group (RANO) criteria, the course of nine patients was classified as initial progressive disease (PD), whereas seven patients presented with initial stable disease (SD), two of which with PsPD
Patients with initial PD showed a tendency toward higher age, lower Karnofsky Performance Index (KPI) and fewer gross tumor resections, but no statistically significant differences were found between the initial PD and initial SD group concerning clinical baseline parameters

Summary

Introduction

The overall prognosis of glioblastoma (GBM) remains poor despite gross tumor resection followed by chemoradiotherapy (CRT), but long-term survival can be achieved in a small subgroup of patients (Stupp et al, 2005, 2009). Current assessment of response to therapy is based on the updated response assessment in neuro-oncology working group (RANO) criteria, which classify clinical follow-up MRI (Wen et al, 2010; Johnson et al, 2019). This approach suffers essential limitations due to the incidence of pseudo-progressions (PsPD) especially shortly after treatment (de Wit et al, 2004; Wen et al, 2010). Imaging techniques that enable an early or even real-time response assessment to guide therapy protocols are highly desirable

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