Volume of high-risk intratumoral subregions at multi-parametric MR imaging predicts overall survival and complements molecular analysis of glioblastoma.
OBJECTIVE
To develop and validate a volume-based, quantitative imaging marker by integrating multi-parametric MR images for predicting glioblastoma survival, and to investigate its relationship and synergy with molecular characteristics.


METHODS
We retrospectively analysed 108 patients with primary glioblastoma. The discovery cohort consisted of 62 patients from the cancer genome atlas (TCGA). Another 46 patients comprising 30 from TCGA and 16 internally were used for independent validation. Based on integrated analyses of T1-weighted contrast-enhanced (T1-c) and diffusion-weighted MR images, we identified an intratumoral subregion with both high T1-c and low ADC, and accordingly defined a high-risk volume (HRV). We evaluated its prognostic value and biological significance with genomic data.


RESULTS
On both discovery and validation cohorts, HRV predicted overall survival (OS) (concordance index: 0.642 and 0.653, P < 0.001 and P = 0.038, respectively). HRV stratified patients within the proneural molecular subtype (log-rank P = 0.040, hazard ratio = 2.787). We observed different OS among patients depending on their MGMT methylation status and HRV (log-rank P = 0.011). Patients with unmethylated MGMT and high HRV had significantly shorter survival (median survival: 9.3 vs. 18.4 months, log-rank P = 0.002).


CONCLUSIONS
Volume of the high-risk intratumoral subregion identified on multi-parametric MRI predicts glioblastoma survival, and may provide complementary value to genomic information.


CONCLUSIONS
• High-risk volume (HRV) defined on multi-parametric MRI predicted GBM survival. • The proneural molecular subtype tended to harbour smaller HRV than other subtypes. • Patients with unmethylated MGMT and high HRV had significantly shorter survival. • HRV complements genomic information in predicting GBM survival.
Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd., Palo Alto, CA, 94304, USA. cuiyi@stanford.edu.|Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan. cuiyi@stanford.edu.
Yi
Y
Cui
School of Electrical Engineering and Automation, Tianjin University, Tianjin Shi, China.
Shangjie
S
Ren
Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan.|Department of Radiology and Nuclear Medicine, Hokkaido University, Hokkaido, Japan.
Khin Khin
KK
Tha
Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd., Palo Alto, CA, 94304, USA.
Jia
J
Wu
Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan.|Department of Radiology and Nuclear Medicine, Hokkaido University, Hokkaido, Japan.
Hiroki
H
Shirato
Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd., Palo Alto, CA, 94304, USA.|Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan.
Ruijiang
R
Li
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000235:genetics
D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
Glioblastoma multiforme; High-risk tumour volume; Multi-parametric MRI; Overall survival; Radiogenomics