Clinical measures, radiomics, and genomics offer synergistic value in AI-based prediction of overall survival in patients with glioblastoma

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作者
Anahita Fathi Kazerooni
Sanjay Saxena
Erik Toorens
Danni Tu
Vishnu Bashyam
Hamed Akbari
Elizabeth Mamourian
Chiharu Sako
Costas Koumenis
Ioannis Verginadis
Ragini Verma
Russell T. Shinohara
Arati S. Desai
Robert A. Lustig
Steven Brem
Suyash Mohan
Stephen J. Bagley
Tapan Ganguly
Donald M. O’Rourke
Spyridon Bakas
MacLean P. Nasrallah
Christos Davatzikos
机构
[1] University of Pennsylvania,Center for Biomedical Image Computing and Analytics (CBICA)
[2] University of Pennsylvania,Department of Radiology, Perelman School of Medicine
[3] University of Pennsylvania,Penn Genomic Analysis Core, Perelman School of Medicine
[4] University of Pennsylvania,Penn Statistics in Imaging and Visualization (PennSIVE) Center, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine
[5] University of Pennsylvania,Department of Radiation Oncology, Perelman School of Medicine
[6] University of Pennsylvania,Abramson Cancer Center, Perelman School of Medicine
[7] Perelman School of Medicine at the University of Pennsylvania,Department of Neurosurgery
[8] University of Pennsylvania,Glioblastoma Translational Center of Excellence, Abramson Cancer Center
[9] University of Pennsylvania,Department of Pathology and Laboratory Medicine, Perelman School of Medicine
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摘要
Multi-omic data, i.e., clinical measures, radiomic, and genetic data, capture multi-faceted tumor characteristics, contributing to a comprehensive patient risk assessment. Here, we investigate the additive value and independent reproducibility of integrated diagnostics in prediction of overall survival (OS) in isocitrate dehydrogenase (IDH)-wildtype GBM patients, by combining conventional and deep learning methods. Conventional radiomics and deep learning features were extracted from pre-operative multi-parametric MRI of 516 GBM patients. Support vector machine (SVM) classifiers were trained on the radiomic features in the discovery cohort (n = 404) to categorize patient groups of high-risk (OS < 6 months) vs all, and low-risk (OS ≥ 18 months) vs all. The trained radiomic model was independently tested in the replication cohort (n = 112) and a patient-wise survival prediction index was produced. Multivariate Cox-PH models were generated for the replication cohort, first based on clinical measures solely, and then by layering on radiomics and molecular information. Evaluation of the high-risk and low-risk classifiers in the discovery/replication cohorts revealed area under the ROC curves (AUCs) of 0.78 (95% CI 0.70–0.85)/0.75 (95% CI 0.64–0.79) and 0.75 (95% CI 0.65–0.84)/0.63 (95% CI 0.52–0.71), respectively. Cox-PH modeling showed a concordance index of 0.65 (95% CI 0.6–0.7) for clinical data improving to 0.75 (95% CI 0.72–0.79) for the combination of all omics. This study signifies the value of integrated diagnostics for improved prediction of OS in GBM.
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