Keng LamBlaine S.C. EldredBryan M. KevanMatthew JiJerry J. LouSean T. PiankaWilliam H. YongLinda M. LiauPhioanh L. NghiemphuTimothy F. CloughesyRichard GreenAlbert Lai
Abstract BACKGROUND Patients with isocitrate dehydrogenase (IDH) mutant gliomas have been associated with longer survival time than those with IDH wildtype. Previous studies have also shown the predictive value of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for glioblastoma. However, little is known in the prognostic value of MGMT methylation status for IDH mutant gliomas. METHODS We retrospectively identified IDH mutant gliomas patients from University of California Los Angeles and Kaiser Permanente Los Angeles that had been tested for MGMT methylation status. We performed Kaplan-Meier and Cox regression analyses of overall survival (OS) to compare the MGMT methylated versus MGMT unmethylated patients. RESULTS We identified a total of 375 IDH mutant gliomas with MGMT testing. Subgroups include 52 glioblastoma, 191 astrocytoma, and 132 oligodendroglioma. The median OS for all MGMT methylated patients was 20.0 years and for unmethylated patients 14.3 years (log-rank P=0.008). Cox regression analysis also confirmed patients with MGMT methylated to have better survival than those with MGMT unmethylated (hazard ratio of 0.47, P= 0.005). During subgroup analysis, MGMT methylated glioblastoma patients have a median OS of 13.7 years compared to MGMT unmethylated patients 3.2 years (log-rank P=0.004) with a hazard ratio of 0.14 (P=0.005). However, we see no difference yet for astrocytoma (hazard ratio of 1.09, P= 0.81) and oligodendrogliomas (hazard ratio of 0.36, P= 0.193), possibly as a result of immature survival data. CONCLUSIONS MGMT promoter methylation is associated with better outcomes in IDH mutant glioblastoma patients. Progression free survival will be analyzed to determine predictive benefit of MGMT methylation for other glioma subtypes.
Gilbert YoussefElisa AquilantiAlona MuzikanskyJulie J. MillerJayne VogelzangEmily LapinskasMary Jane Lim-FatRifaquat RahmanRameen BeroukhimWenya Linda BiUgonma ChukwuekeL. Nicolas Gonzalez CastroEudocia Q. LeeJ Ricardo McFaline-FigueroaLakshmi NayakDavid A. ReardonKeith L. LigonPatrick Y. Wen
Mark Willy L. MondiaMu-Hsun ChenHong ZhuJasmin JoDavid Schiff
Waqar HaqueElaine ThongSara AndrabiVivek VermaE. Brian ButlerBin S. Teh
Enrico FranceschiAlicia TosoniVincenzo Di NunnoAntonella MuraSofia AsioliAnnalisa PessionR. AgatiAlexandro PaccapeloStefania BartoliniAlba A. Brandes
Gilbert YoussefElisa AquilantiJulie J. MillerZhou LanAleksandra B LasicaIsabel Arrillaga‐RomanyTracy T. BatchelorTamar BergerRameen BeroukhimUgonma ChukwuekeJörg DietrichDeborah ForstElizabeth R. GerstnerL. Nicolas Gonzalez CastroJustin T. JordanJ Ricardo McFaline-FigueroaEudocia Q. LeeLakshmi NayakVihang NakhateJuan Pablo OspinaScott R. PlotkinNancy WangJohn Y. RheeDavid A. ReardonPatrick Y. Wen