Validation of diffusion MRI phenotypes for predicting response to bevacizumab in recurrent glioblastoma: post-hoc analysis of the EORTC-26101 trial.,Neuro-Oncology

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Validation of diffusion MRI phenotypes for predicting response to bevacizumab in recurrent glioblastoma: post-hoc analysis of the EORTC-26101 trial.
Neuro-Oncology ( IF 16.4 ) Pub Date : null , DOI: 10.1093/neuonc/noaa120
Marianne Schell _{1,

2} , Irada Pflüger _{1,

2} , Gianluca Brugnara _{1,

2} , Fabian Isensee ₃ , Ulf Neuberger _{1,

2,

3} , Martha Foltyn _{1,

2} , Tobias Kessler _{4,

5} , Felix Sahm _{6,

7} , Antje Wick ₄ , Martha Nowosielski _{4,

7,

8} , Sabine Heiland ₁ , Michael Weller ₉ , Michael Platten ₁₀ , Klaus H Maier-Hein _{3,

10} , Andreas Von Deimling _{6,

7} , Martin J Van Den Bent ₁₁ , Thierry Gorlia ₁₂ , Wolfgang Wick _{4,

5,

7} , Martin Bendszus ₁ , Philipp Kickingereder _{1,

2}

Affiliation

Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
Section for Computational Neuroimaging, Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
Medical Image Computing, German Cancer Research Center, Heidelberg, Germany.
Neurology Clinic, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neurooncology, German Cancer Research Center, Heidelberg, Germany.
Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany.
Department of Neurology, Medical University, Innsbruck, Austria.
Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Department of Neurology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, Netherlands.
European Organisation for Research and Treatment of Cancer, Brussels, Belgium.

Abstract

Background

This study validated a previously described diffusion MRI phenotype as a potential predictive imaging biomarker in patients with recurrent glioblastoma receiving bevacizumab (BEV).

Methods

A total of 396/596 patients (66%) from the prospective randomized phase II/III EORTC-26101 trial (with n = 242 in the BEV and n = 154 in the non-BEV arm) met the inclusion criteria with availability of anatomical and diffusion MRI sequences at baseline prior treatment. Apparent diffusion coefficient (ADC) histograms from the contrast-enhancing tumor volume were fitted to a double Gaussian distribution and the mean of the lower curve (ADC_low) was used for further analysis. The predictive ability of ADC_low was assessed with biomarker threshold models and multivariable Cox regression for overall survival (OS) and progression-free survival (PFS).

Results

ADC_low was associated with PFS (hazard ratio [HR] = 0.625, P = 0.007) and OS (HR = 0.656, P = 0.031). However, no (predictive) interaction between ADC_low and the treatment arm was present (P = 0.865 for PFS, P = 0.722 for OS). Independent (prognostic) significance of ADC_low was retained after adjusting for epidemiological, clinical, and molecular characteristics (P ≤ 0.02 for OS, P ≤ 0.01 PFS). The biomarker threshold model revealed an optimal ADC_low cutoff of 1241*10–6 mm²/s for OS. Thereby, median OS for BEV-patients with ADC_low ≥ 1241 was 10.39 months versus 8.09 months for those with ADC_low< 1241 (P = 0.004). Similarly, median OS for non-BEV patients with ADC_low≥ 1241 was 9.80 months versus 7.79 months for those with ADC_low < 1241 (P = 0.054).

Conclusions

ADC_low is an independent prognostic parameter for stratifying OS and PFS in patients with recurrent glioblastoma. Consequently, the previously suggested role of ADC_low as predictive imaging biomarker could not be confirmed within this phase II/III trial.

更新日期：2020-11-27

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