Relationship between tumor enhancement, edema, IDH1 mutational status, MGMT promoter methylation, and survival in glioblastoma.
OBJECTIVE
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.


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.
Department of Neurology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, BL-428 CHS, Los Angeles, CA 90095-1721, USA.
J A
JA
Carrillo
A
A
Lai
P L
PL
Nghiemphu
H J
HJ
Kim
H S
HS
Phillips
S
S
Kharbanda
P
P
Moftakhar
S
S
Lalaezari
W
W
Yong
B M
BM
Ellingson
T F
TF
Cloughesy
W B
WB
Pope
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001929:Brain Edema / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D002140:California / Q000453:epidemiology; D015897:Comorbidity; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013223:Statistics as Topic; D016019:Survival Analysis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes