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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.


Schell, Marianne; Pflüger, Irada; Brugnara, Gianluca; Isensee, Fabian; Neuberger, Ulf; Foltyn, Martha; Kessler, Tobias; Sahm, Felix; Wick, Antje; Nowosielski, Martha; Heiland, Sabine; Weller, Michael; Platten, Michael; Maier-Hein, Klaus H; von Deimling, Andreas; van den Bent, Martin J; Gorlia, Thierry; Wick, Wolfgang; Bendszus, Martin; Kickingereder, Philipp (2020). Validation of diffusion MRI phenotypes for predicting response to bevacizumab in recurrent glioblastoma: post-hoc analysis of the EORTC-26101 trial. Neuro-Oncology, 22(11):1667-1676.

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 (ADClow) was used for further analysis. The predictive ability of ADClow was assessed with biomarker threshold models and multivariable Cox-regression for overall and progression-free survival (OS, PFS).
RESULTS: ADClow was associated with PFS (HR=0.625,p=0.007) and OS (HR=0.656,p=0.031). However, no (predictive) interaction between ADClow and the treatment arm was present (p=0.865 for PFS, p=0.722 for OS). Independent (prognostic) significance of ADClow 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 ADClow cutoff of 1241*10-6mm²/s for OS. Thereby, median OS for BEV-patients with ADClow≥1241 was 10.39 months vs. 8.09 months for those with ADClow<1241 (p=0.004). Similarly, median OS for non-BEV patients with ADClow≥1241 was 9.80 months vs. 7.79 months for those with ADClow<1241 (p=0.054).
CONCLUSIONS: ADClow is an independent prognostic parameter for stratifying OS and PFS in patients with recurrent glioblastoma. Consequently, the previously suggested role of ADClow as predictive imaging biomarker could not be confirmed within this phase II/III trial.

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 (ADClow) was used for further analysis. The predictive ability of ADClow was assessed with biomarker threshold models and multivariable Cox-regression for overall and progression-free survival (OS, PFS).
RESULTS: ADClow was associated with PFS (HR=0.625,p=0.007) and OS (HR=0.656,p=0.031). However, no (predictive) interaction between ADClow and the treatment arm was present (p=0.865 for PFS, p=0.722 for OS). Independent (prognostic) significance of ADClow 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 ADClow cutoff of 1241*10-6mm²/s for OS. Thereby, median OS for BEV-patients with ADClow≥1241 was 10.39 months vs. 8.09 months for those with ADClow<1241 (p=0.004). Similarly, median OS for non-BEV patients with ADClow≥1241 was 9.80 months vs. 7.79 months for those with ADClow<1241 (p=0.054).
CONCLUSIONS: ADClow is an independent prognostic parameter for stratifying OS and PFS in patients with recurrent glioblastoma. Consequently, the previously suggested role of ADClow as predictive imaging biomarker could not be confirmed within this phase II/III trial.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Oncology
Health Sciences > Neurology (clinical)
Life Sciences > Cancer Research
Language:English
Date:11 May 2020
Deposited On:14 Dec 2020 17:35
Last Modified:15 Dec 2020 21:00
Publisher:Oxford University Press
ISSN:1522-8517
Additional Information:This is a pre-copyedited, author-produced PDF of an article accepted for publication in Neuro-Oncology following peer review. The definitive publisher-authenticated version Schell M, Pflüger I, Brugnara G, Isensee F, Neuberger U, Foltyn M, Kessler T, Sahm F, Wick A, Nowosielski M, Heiland S, Weller M, Platten M, Maier-Hein KH, Von Deimling A, Van Den Bent MJ, Gorlia T, Wick W, Bendszus M, Kickingereder P. Validation of diffusion MRI phenotypes for predicting response to bevacizumab in recurrent glioblastoma: post-hoc analysis of the EORTC-26101 trial. Neuro Oncol. 2020 Nov 26;22(11):1667-1676. doi: 10.1093/neuonc/noaa120.
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/neuonc/noaa120
PubMed ID:32393964

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