Prognostic Imaging Biomarkers in Glioblastoma: Development and Independent Validation on the Basis of Multiregion and Quantitative Analysis of MR Images.
OBJECTIVE
To develop and independently validate prognostic imaging biomarkers for predicting survival in patients with glioblastoma on the basis of multiregion quantitative image analysis.


METHODS
This retrospective study was approved by the local institutional review board, and informed consent was waived. A total of 79 patients from two independent cohorts were included. The discovery and validation cohorts consisted of 46 and 33 patients with glioblastoma from the Cancer Imaging Archive (TCIA) and the local institution, respectively. Preoperative T1-weighted contrast material-enhanced and T2-weighted fluid-attenuation inversion recovery magnetic resonance (MR) images were analyzed. For each patient, we semiautomatically delineated the tumor and performed automated intratumor segmentation, dividing the tumor into spatially distinct subregions that demonstrate coherent intensity patterns across multiparametric MR imaging. Within each subregion and for the entire tumor, we extracted quantitative imaging features, including those that fully capture the differential contrast of multimodality MR imaging. A multivariate sparse Cox regression model was trained by using TCIA data and tested on the validation cohort.


RESULTS
The optimal prognostic model identified five imaging biomarkers that quantified tumor surface area and intensity distributions of the tumor and its subregions. In the validation cohort, our prognostic model achieved a concordance index of 0.67 and significant stratification of overall survival by using the log-rank test (P = .018), which outperformed conventional prognostic factors, such as age (concordance index, 0.57; P = .389) and tumor volume (concordance index, 0.59; P = .409).


CONCLUSIONS
The multiregion analysis presented here establishes a general strategy to effectively characterize intratumor heterogeneity manifested at multimodality imaging and has the potential to reveal useful prognostic imaging biomarkers in glioblastoma.
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Yi
Y
Cui
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Khin Khin
KK
Tha
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Shunsuke
S
Terasaka
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Shigeru
S
Yamaguchi
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Jeff
J
Wang
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Kohsuke
K
Kudo
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Lei
L
Xing
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Hiroki
H
Shirato
From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).
Ruijiang
R
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D003287:Contrast Media; D005260:Female; D005909:Glioblastoma / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D003287:Contrast Media