RT Journal Article
SR Electronic
T1 Relationship between Tumor Enhancement, Edema, <em>IDH1</em> Mutational Status, <em>MGMT</em> Promoter Methylation, and Survival in Glioblastoma
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
SP 1349
OP 1355
DO 10.3174/ajnr.A2950
VO 33
IS 7
A1 J.A. Carrillo
A1 A. Lai
A1 P.L. Nghiemphu
A1 H.J. Kim
A1 H.S. Phillips
A1 S. Kharbanda
A1 P. Moftakhar
A1 S. Lalaezari
A1 W. Yong
A1 B.M. Ellingson
A1 T.F. Cloughesy
A1 W.B. Pope
YR 2012
UL http://www.ajnr.org/content/33/7/1349.abstract
AB BACKGROUND AND PURPOSE: Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly defined GBM subtypes. MATERIALS AND METHODS: MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features. RESULTS: MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507–654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation. CONCLUSIONS: Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival. CI confidence intervalGBM glioblastoma multiformeIDH1isocitrate dehydrogenase-1IQR interquartile rangeMGMTO-6-methylguanine-DNA-methyltransferaseOR odds rationCET non-contrast enhancing tumorPCR polymerase chain reactionROC receiver operator curve