Radiomic subtyping improves disease stratification beyond key molecular, clinical and standard imaging characteristics in patients with glioblastoma.

Background: To analyze the potential of radiomics for disease stratification beyond key molecular, clinical and standard imaging features in patients with glioblastoma. Methods: Quantitative imaging features (n=1043) were extracted from the multiparametric MRI of 181 patients with newly-diagnosed glioblastoma prior to standard-of-care treatment (allocated to a discovery and validation set, 2:1 ratio). A subset of 386/1043 features were identified as reproducible (in an independent MRI-test-retest cohort) and selected for analysis. A penalized Cox-model with 10-fold cross-validation (Coxnet) was fitted on the discovery set to construct a radiomic signature for predicting progression-free and overall survival (PFS, OS). The incremental value of a radiomic signature beyond molecular (MGMT-promoter methylation, DNA-methylation subgroups), clinical (patients age, KPS, extent-of-resection, adjuvant treatment) and standard imaging parameters (tumor volumes) for stratifying PFS and OS was assessed with multivariate Cox-models (performance quantified with prediction error curves). Results: The radiomic signature (constructed from 8/386 features identified through Coxnet) increased the prediction accuracy for PFS and OS (in both discovery and validation set) beyond the assessed molecular, clinical and standard imaging parameters (p≤0.01). Prediction errors decreased by 36% for PFS and 37% for OS when adding the radiomic signature (as compared to 29% and 27% with molecular + clinical features alone). The radiomic signature was - along with MGMT-status - the only parameter with independent significance on multivariate analysis (p≤0.01). Conclusions: Our study stresses the role of integrating radiomics into a multi-layer decision framework with key molecular and clinical features to improve disease stratification and to potentially advance personalized treatment of patients with glioblastoma. The Illumina Infinium HumanMethylation450 array (Illumina, San Diego, USA) data from n=181 patients were used to obtain genome-wide assessment of DNA methylation, according to the manufacturer’s instructions at the Genomics and Proteomics Core Facility of the German Cancer Research Center (DKFZ) as described previously (Sturm et al. Cancer Cell. 2012 Oct 16;22(4):425-37)