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Background The biologic meaning of prognostic radiomics phenotypes remains poorly understood, hampered in part by lack of multicenter reproducible evidence. Purpose To uncover the biologic meaning of individual prognostic radiomics phenotypes in glioblastomas using paired MRI and RNA sequencing data and to validate the reproducibility of the identified radiogenomics linkages externally. Materials and Methods This retrospective multicenter study included four data sets gathered between January 2015 and December 2016. From a radiomics analysis set, a 13-feature radiomics signature was built using preoperative MRI for overall survival prediction. Using a radiogenomics training set with both MRI and RNA sequencing, biologic pathways were enriched and correlated with each of the 13 radiomics phenotypes. Radiomics-correlated key genes were identified to derive a prognostic radiomics gene expression (RadGene) score. The reproducibility of identified pathways and genes was validated with an external test set and a public data set (The Cancer Genome Atlas [TCGA]). A log-rank test was performed to assess prognostic significance. Results A total of 435 patients (mean age, 55 years ± 15 [standard deviation]; 263 men) were enrolled. The radiomics signature was associated with overall survival (hazard ratio [HR], 3.68; 95% CI: 2.08, 6.52; P < .001) in the radiomics validation subset. Four types of prognostic radiomics phenotypes were correlated with distinct pathways: immune, proliferative, treatment responsive, and cellular functions (false-discovery rate < 0.10). Thirty radiomics-correlated genes were identified. The prognostic significance of the RadGene score was confirmed in an external test set (HR, 2.02; 95% CI: 1.19, 3.41; P = .01) and a TCGA test set (HR, 1.43; 95% CI: 1.001, 2.04; P = .048). The radiomics-associated pathways and key genes can be replicated in an external test set. Conclusion Individual radiomics phenotypes on MRI scans predictive of overall survival were driven by distinct key pathways involved in immune regulation, tumor proliferation, treatment responses, and cellular functions in glioblastoma, which could be reproduced externally. © RSNA, 2021 Online supplemental material is available for this article.

Purpose: Isocitrate dehydrogenase 1 (IDH1) has been proven as a prognostic and predictive marker in glioblastoma (GBM) patients. The purpose was to preoperatively predict IDH mutation status in GBM using multiregional radiomics features from multiparametric magnetic resonance imaging (MRI)., Methods: In this retrospective multicenter study, 225 patients were included. A total of 1614 multiregional features were extracted from enhancement area, non-enhancement area, necrosis, edema, tumor core, and whole tumor in multiparametric MRI. Three multiregional radiomics models were built from tumor core, whole tumor, and all regions using an all-relevant feature selection and a random forest classification for predicting IDH1. Four single-region models and a model combining all-region features with clinical factors (age, sex, and Karnofsky performance status) were also built. All models were built from a training cohort (118 patients) and tested on an independent validation cohort (107 patients)., Results: Among the four single-region radiomics models, the edema model achieved the best accuracy of 96% and the best F1-score of 0.75 while the non-enhancement model achieved the best area under the receiver operating characteristic curve (AUC) of 0.88 in the validation cohort. The overall performance of the tumor-core model (accuracy 0.96, AUC 0.86 and F1-score 0.75) and the whole-tumor model (accuracy 0.96, AUC 0.88 and F1-score 0.75) was slightly better than the single-regional models. The 8-feature all-region radiomics model achieved an improved overall performance of an accuracy 96%, an AUC 0.90, and an F1-score 0.78. Among all models, the model combining all-region imaging features with age achieved the best performance of an accuracy 97%, an AUC 0.96, and an F1-score 0.84., Conclusions: The radiomics model built with multiregional features from multiparametric MRI has the potential to preoperatively detect the IDH1 mutation status in GBM patients. The multiregional model built with all-region features performed better than the single-region models, while combining age with all-region features achieved the best performance., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To develop and validate a deep learning imaging signature (DLIS) for risk stratification in patients with multiforme (GBM), and to investigate the biological pathways and genetic alterations underlying the DLIS. Methods: The DLIS was developed from multi-parametric MRI based on a training set (n = 600) and validated on an internal validation set (n = 164), an external test set 1 (n = 100), an external test set 2 (n = 161), and a public TCIA set (n = 88). A co-profiling framework based on a radiogenomics analysis dataset (n = 127) using multiscale high-dimensional data, including imaging, transcriptome, and genome, was established to uncover the biological pathways and genetic alterations underpinning the DLIS. Results: The DLIS was associated with survival (log-rank p < 0.001) and was an independent predictor (p < 0.001). The integrated nomogram incorporating the DLIS achieved improved C indices than the clinicomolecular nomogram (net reclassification improvement 0.39, p < 0.001). DLIS significantly correlated with core pathways of GBM (apoptosis and cell cycle-related P53 and RB pathways, and cell proliferation-related RTK pathway), as well as key genetic alterations (del_CDNK2A). The prognostic value of DLIS-correlated genes was externally confirmed on TCGA/CGGA sets (p < 0.01). Conclusions: Our study offers a biologically interpretable deep learning predictor of survival outcomes in patients with GBM, which is crucial for better understanding GBM patient's prognosis and guiding individualized treatment. Key Points: • MRI-based deep learning imaging signature (DLIS) stratifies GBM into risk groups with distinct molecular characteristics. • DLIS is associated with P53, RB, and RTK pathways and del_CDNK2A mutation. • The prognostic value of DLIS-correlated pathway genes is externally demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: To build a reliable radiomics model from multiregional and multiparametric magnetic resonance imaging (MRI) for pretreatment prediction of O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status in glioblastoma multiforme (GBM).Methods: In this retrospective multicentre study, 1,705 multiregional radiomics features were automatically extracted from multiparametric MRI. A radiomics model with a minimal set of all-relevant features and a radiomics model with univariately-predictive and non-redundant features were built for MGMT methylation prediction from a primary cohort (133 patients) and tested on an independent validation cohort (60 patients). Predictive models combing clinical factors were built and evaluated. Both radiomics models were assessed on subgroups stratified by clinical factors.Results: The radiomics model with six all-relevant features allowed pretreatment prediction of MGMT methylation (AUC=0.88, accuracy=80 %), which significantly outperformed the model with eight univariately-predictive and non-redundant features (AUC=0.76, accuracy=70 %). Combing clinical factors with radiomics features did not benefit the prediction performance. The all-relevant model achieved significantly better performance in stratified analysis.Conclusions: Radiomics model built from multiregional and multiparameter MRI may serve as a potential imaging biomarker for pretreatment prediction of MGMT methylation in GBM. The all-relevant features have the potential of offering better predictive power than the univariately-predictive and non-redundant features.Key Points: • Multiregional and multiparametric MRI features reliably predicted MGMT methylation in multicentre cohorts. • All-relevant imaging features predicted MGMT methylation better than univariately-predictive and non-redundant features. • Combing clinical factors with radiomics features did not benefit the prediction performance. [ABSTRACT FROM AUTHOR]