2023
MGMT Promoter Methylation Predicts Survival in 1p19q-Codeleted Gliomas after Chemotherapy
Kinslow C, Rae A, Kumar P, Grinband J, Gill B, McKhann G, Sisti M, Bruce J, Canoll P, Iwamoto F, Yu J, Kachnic L, Cheng S, Wang T. MGMT Promoter Methylation Predicts Survival in 1p19q-Codeleted Gliomas after Chemotherapy. International Journal Of Radiation Oncology • Biology • Physics 2023, 117: e117. DOI: 10.1016/j.ijrobp.2023.06.902.Peer-Reviewed Original ResearchMGMT promoter methylationMGMT promoter statusMGMT promoter methylation statusAssociated with poor survivalNational Cancer DatabaseOverall survivalUnmethylated MGMTPromoter methylation statusPromoter methylationPromoter statusAlkylating chemotherapyPoor survivalMultivariate Cox proportional hazards regression modelsResponse to alkylating chemotherapyProgression-free survivalCox proportional hazards regression modelsMethylation statusProportional hazards regression modelsReceipt of chemotherapyHazards regression modelsCourse of treatmentAnaplastic gliomasMGMT promoterCancer DatabaseDiagnosed gliomasMGMT Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas.
Kinslow C, Rae A, Taparra K, Kumar P, Siegelin M, Grinband J, Gill B, McKhann G, Sisti M, Bruce J, Canoll P, Iwamoto F, Horowitz D, Kachnic L, Neugut A, Yu J, Cheng S, Wang T. MGMT Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas. Clinical Cancer Research 2023, 29: 4399-4407. PMID: 37611077, PMCID: PMC10872921, DOI: 10.1158/1078-0432.ccr-23-1295.Peer-Reviewed Original ResearchConceptsAssociated with worse survivalOverall survivalMGMT promoter statusUnmethylated MGMTWorse survivalPrognostic of progression-free survivalPromoter statusMultivariate Cox proportional hazards regression modelsWorld Health Organization gradeProgression-free survivalNational Cancer DatabaseCox proportional hazards regression modelsMGMT promoter methylationProportional hazards regression modelsGuiding treatment decisionsHazards regression modelsCourse of treatmentPredictive of responseMultiagent chemotherapyMGMT promoterCancer DatabaseMMGMTAlkylating chemotherapyChemotherapyEligible patients
2022
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter
Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro-Oncology 2022, 24: 1935-1949. PMID: 35511454, PMCID: PMC9629431, DOI: 10.1093/neuonc/noac116.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalMGMT promoterBaseline corticosteroidsTreatment-related adverse event ratesImmune checkpoint inhibitor nivolumabNew safety signalsPhase III trialsAdverse event ratesCheckpoint inhibitor nivolumabCare radiotherapyInhibitor nivolumabPrimary endpointIII trialsSame regimenExperience recurrenceNivolumabSafety signalsPlaceboPatientsRadiotherapyTemozolomideEvent ratesMonthsPhase IIIRadiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial
Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro-Oncology 2022, 25: 123-134. PMID: 35419607, PMCID: PMC9825306, DOI: 10.1093/neuonc/noac099.Peer-Reviewed Original ResearchConceptsOverall survivalUnmethylated MGMT promoterMedian OSPrimary endpointInternational randomized phase III trialTreatment-related adverse event ratesMedian progression-free survivalRandomized phase III trialMGMT promoterEfficacy of nivolumabLonger median OSMedian overall survivalNew safety signalsProgression-free survivalAddition of temozolomideAdverse event ratesPhase III trialsUse of temozolomideStandard of careStudy treatment armsImproved OSIII trialsTreatment armsStandard radiotherapyNivolumab
2021
CTIM-25. A RANDOMIZED PHASE 3 STUDY OF NIVOLUMAB OR PLACEBO COMBINED WITH RADIOTHERAPY PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA WITH METHYLATED MGMT PROMOTER: CHECKMATE 548
Weller M, Lim M, Idbaih A, Steinbach J, Finocchiaro G, Raval R, Ashby L, Ansstas G, Baehring J, Taylor J, Honnorat J, Petrecca K, de Vos F, Wick A, Sumrall A, Roberts M, Slepetis R, Warad D, Lee M, Reardon D, Omuro A. CTIM-25. A RANDOMIZED PHASE 3 STUDY OF NIVOLUMAB OR PLACEBO COMBINED WITH RADIOTHERAPY PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA WITH METHYLATED MGMT PROMOTER: CHECKMATE 548. Neuro-Oncology 2021, 23: vi55-vi56. PMCID: PMC8598415, DOI: 10.1093/neuonc/noab196.217.Peer-Reviewed Original ResearchProgression-free survivalMedian overall survivalPhase 3 studyOverall survivalMGMT promoterBaseline corticosteroidsMedian progression-free survivalTreatment-related adverse eventsRandomized phase 3 studyTumor PD-L1 expressionBlinded independent central reviewDual primary endpointsRole of immunotherapyNew safety signalsPD-L1 expressionPositive prognostic factorIndependent central reviewPredictors of benefitCare radiotherapyTreatment landscapeAdverse eventsPrognostic factorsCentral reviewNivolumabNovel therapies
2014
Transcriptional diversity of long-term glioblastoma survivors
Gerber NK, Goenka A, Turcan S, Reyngold M, Makarov V, Kannan K, Beal K, Omuro A, Yamada Y, Gutin P, Brennan CW, Huse JT, Chan TA. Transcriptional diversity of long-term glioblastoma survivors. Neuro-Oncology 2014, 16: 1186-1195. PMID: 24662514, PMCID: PMC4136896, DOI: 10.1093/neuonc/nou043.Peer-Reviewed Original ResearchConceptsMemorial Sloan-Kettering Cancer CenterLong-term survivorsLong-term glioblastoma survivorsIDH mutationsIDH2 mutational statusMedian overall survivalStrong prognostic valueBiology of glioblastomaMGMT promoter methylationMedian survivalOverall survivalBetter prognosisPoor prognosisPrognostic valueCancer CenterAggressive typeIndependent cohortMesenchymal subtypeREMBRANDT cohortMutational statusIDH2 mutationsGBM biologyPatientsMGMT methylationMGMT promoter
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