2023
Top advances of the year: Neuro‐oncology
Barden M, Omuro A. Top advances of the year: Neuro‐oncology. Cancer 2023, 129: 1467-1472. PMID: 36825454, DOI: 10.1002/cncr.34711.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBrain tumorsRecent phase 3 trialAnti-PD-1 immunotherapyCentral nervous system dysfunctionSingle-agent pembrolizumabHigh-dose chemotherapyPhase 3 trialPrimary CNS lymphomaStem cell transplantationLong-term outcomesLimited therapeutic optionsNervous system dysfunctionOngoing clinical trialsClinical trial landscapeDrug Administration approvalBRAF V600E mutationExcellent disease controlConsolidation therapyCNS lymphomaImproved survivalLeptomeningeal metastasesTherapeutic optionsCell transplantationCraniospinal irradiationPatient populationMulticenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
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 IIIImmune-checkpoint inhibitors for glioblastoma: what have we learned?
Omuro A. Immune-checkpoint inhibitors for glioblastoma: what have we learned? Arquivos De Neuro-Psiquiatria 2022, 80: 266-269. PMID: 35976319, PMCID: PMC9491432, DOI: 10.1590/0004-282x-anp-2022-s129.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRecurrent glioblastomaBrain tumorsRandomized phase 3 trialCommon malignant primary brain tumorPost-treatment tumor samplesMalignant primary brain tumorSuccessful immunotherapeutic approachesPhase 3 trialPhase 1 studySelection of patientsT cell dysfunctionNew safety concernsHigh mutational burdenPrimary brain tumorsCheckpoint inhibitorsRadiographic responseImmunotherapeutic approachesPD-L1Survival improvementImmunologic responseTherapeutic optionsClinical trialsCNS microenvironmentCell dysfunctionRadiotherapy 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
T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies
Jansen JA, Omuro A, Lucca LE. T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies. Current Opinion In Neurology 2021, 34: 827-833. PMID: 34569985, PMCID: PMC8595795, DOI: 10.1097/wco.0000000000000988.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCentral Nervous SystemGlioblastomaHumansImmunotherapyMiceT-LymphocytesConceptsT cell dysfunctionTumor-infiltrating T cellsT cellsCell dysfunctionFuture immunotherapy strategiesCervical lymph nodesTumor-derived antigensImmune checkpoint blockadeCentral nervous systemHomeostatic brainSuccessful immunotherapyCheckpoint blockadeImmunotherapy strategiesLymph nodesTumor rejectionImmune surveillanceImmune responseMouse modelBrain tumorsLymphatic drainageNervous systemSolid tumorsDysfunctionSingle-cell RNA sequencingNatural historyComparison of radiomic feature aggregation methods for patients with multiple tumors
Chang E, Joel MZ, Chang HY, Du J, Khanna O, Omuro A, Chiang V, Aneja S. Comparison of radiomic feature aggregation methods for patients with multiple tumors. Scientific Reports 2021, 11: 9758. PMID: 33963236, PMCID: PMC8105371, DOI: 10.1038/s41598-021-89114-6.Peer-Reviewed Original ResearchConceptsCox proportional hazards modelCox proportional hazardsProportional hazards modelBrain metastasesRadiomic featuresHazards modelProportional hazardsStandard Cox proportional hazards modelMultifocal brain metastasesMultiple brain metastasesNumber of patientsPatient-level outcomesHigher concordance indexRadiomic feature analysisRandom survival forest modelSurvival modelsDifferent tumor volumesMultifocal tumorsCancer outcomesMultiple tumorsMetastatic cancerConcordance indexTumor volumePatientsTumor types
2020
A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma
Gilbert MR, Yuan Y, Wu J, Mendoza T, Vera E, Omuro A, Lieberman F, Robins HI, Gerstner ER, Wu J, Wen PY, Mikkelsen T, Aldape K, Armstrong TS. A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma. Neuro-Oncology 2020, 23: 468-477. PMID: 33085768, PMCID: PMC7992893, DOI: 10.1093/neuonc/noaa240.Peer-Reviewed Original ResearchConceptsProgression-free survivalDose-dense temozolomideMedian progression-free survivalAdult patientsObjective responseSymptom burdenClinical trialsRecurrent ependymomaMD Anderson Symptom Inventory-Brain TumorProspective phase II clinical trialMedian Karnofsky performance statusPhase II clinical trialDemonstrated clinical activityModerate-severe painPatients age 18Phase II studyKarnofsky performance statusProspective clinical trialsSpinal cord tumorsStandard medical treatmentPrimary outcome measureSpinal cord ependymomasDisease-related symptomsExpression of ErbB2Daily lapatinibEffect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma
Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma. JAMA Oncology 2020, 6: 1003-1010. PMID: 32437507, PMCID: PMC7243167, DOI: 10.1001/jamaoncol.2020.1024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntineoplastic Agents, ImmunologicalBevacizumabBrain NeoplasmsDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasm Recurrence, LocalNivolumabProgrammed Cell Death 1 ReceptorTemozolomideTreatment OutcomeTumor Suppressor ProteinsYoung AdultConceptsTreatment-related adverse eventsPhase 3 clinical trialsPrimary end pointOverall survivalRecurrent glioblastomaClinical trialsMedian OSGrade 3/4 treatment-related adverse eventsRandomized phase 3 clinical trialSingle-agent PD-1 blockadeEnd pointEffects of nivolumabUnacceptable toxic effectsMedian overall survivalObjective response ratePD-1 blockadeOverall patient populationImmune checkpoint blockadeData cutoffAdverse eventsCheckpoint blockadeFirst recurrenceInhibitor therapyClinical outcomesSafety profilePhase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapy
2019
Complications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatientsApplications of artificial intelligence in neuro-oncology.
Aneja S, Chang E, Omuro A. Applications of artificial intelligence in neuro-oncology. Current Opinion In Neurology 2019, 32: 850-856. PMID: 31609739, DOI: 10.1097/wco.0000000000000761.Peer-Reviewed Original ResearchMeSH KeywordsArtificial IntelligenceBiomarkers, TumorBrain NeoplasmsGenomicsHumansMedical OncologyNeuroimagingNeurologyConceptsArtificial intelligenceArtificial intelligence algorithmsNatural language processingAmount of dataIntelligence algorithmsLanguage processingIntelligenceNeuro-oncologyImage analysisApplicationsAlgorithmRisk stratificationFuture innovationsTreatment responseBrain tumorsClinical practiceClassificationRecent applicationsProcessingSignificant promiseChallengesDetectionImaging biomarkers for brain metastases: more than meets the eye
Aneja S, Omuro A. Imaging biomarkers for brain metastases: more than meets the eye. Neuro-Oncology 2019, 21: 1493-1494. PMID: 31777936, PMCID: PMC6917408, DOI: 10.1093/neuonc/noz193.Peer-Reviewed Original ResearchBuparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, S. A, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal Of Clinical Oncology 2019, 37: jco.18.01207. PMID: 30715997, PMCID: PMC6553812, DOI: 10.1200/jco.18.01207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic AgentsBrain NeoplasmsChemotherapy, AdjuvantDisease ProgressionEnzyme ActivationFemaleGlioblastomaHumansMaleMiddle AgedMorpholinesNeoadjuvant TherapyNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProgression-Free SurvivalTime FactorsConceptsPhase II trialCohort 2Cohort 1PI3K pathwayTumor tissueII trialRecurrent glioblastomaBrain penetrationPan-PI3K inhibitor buparlisibPathway inhibitionPathway activationCommon grade 3K pathwayPrimary end pointGreater adverse eventsProgression-free survivalPI3K pathway inhibitionPI3K pathway activationPlasma drug levelsSingle-agent efficacySignificant brain penetrationPI3K inhibitorsMedian PFSOpen labelAdverse events
2018
Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.
Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. Journal Of Clinical Oncology 2018, 36: 1702-1709. PMID: 29683790, PMCID: PMC5993168, DOI: 10.1200/jco.2017.76.9992.Peer-Reviewed Original ResearchConceptsAnaplastic gliomasCohort 2Cohort 1Median progression-free survivalFavorable brain penetrationMedian overall survivalPhase Ib studyPhase Ib trialPhase II doseProgression-free survivalRecurrent anaplastic gliomasDependent calcium channelsNovel oral inhibitorSignal of activityMismatch repair genesIb trialTreat populationMethylguanine-DNA methyltransferaseOverall survivalComplete responseFlat doseOral inhibitorBrain penetrationResults FortyTherapeutic concentrationsRadiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab
Thomas A, Rosenblum M, Karimi S, DeAngelis LM, Omuro A, Kaley TJ. Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab. CNS Oncology 2018, 07: 7-13. PMID: 29388793, PMCID: PMC6001559, DOI: 10.2217/cns-2017-0025.Peer-Reviewed Original ResearchConceptsMalignant gliomasRecurrence patternsDiffusion-weighted imaging abnormalitiesDiffusion-weighted imagingStandard clinical settingMG patientsImaging abnormalitiesMRI abnormalitiesPathologic findingsTumor recurrenceRadiographic patternsPathologic correlationBevacizumabClinical settingNecrosisPatientsRecurrenceRecent reportsTumorsGliomasAbnormalitiesLeptomeningealSurgery
2017
Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143
Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampson JH. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology 2017, 20: 674-686. PMID: 29106665, PMCID: PMC5892140, DOI: 10.1093/neuonc/nox208.Peer-Reviewed Original ResearchConceptsAdverse eventsRecurrent glioblastomaCommon treatment-related adverse eventsTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionEffects of nivolumabExploratory efficacy outcomesSafety/tolerabilityFindings merit further investigationLigand 1 expressionCheckMate 143Ipilimumab doseNivolumab monotherapyStable diseaseAlternative regimenEfficacy outcomesRadiographic progressionMost patientsPartial responseNivolumabIpilimumabMerit further investigationPatientsI cohortFurther evaluationMulticenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma
Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. International Journal Of Radiation Oncology • Biology • Physics 2017, 99: 797-804. PMID: 28870792, PMCID: PMC5654655, DOI: 10.1016/j.ijrobp.2017.06.2466.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiogenesis InhibitorsAstrocytomaBevacizumabBrainBrain NeoplasmsFemaleGlioblastomaHumansIntention to Treat AnalysisKarnofsky Performance StatusMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalOrgans at RiskProspective StudiesRadiation Dose HypofractionationRadiosurgeryRe-IrradiationTumor BurdenConceptsRecurrent high-grade gliomaDose-limiting toxicityHigh-grade gliomasStereotactic reirradiationHypofractionated Stereotactic Radiation TherapyCorpus callosum involvementDose level cohortsGrade 3 fatigueMedian overall survivalKarnofsky performance statusDose-escalation studyTreatment-related effectsBiological equivalent doseStereotactic radiation therapyWarrants further investigationAbsence of brainstemDose-escalation trial designBevacizumab dosesCallosum involvementConcomitant bevacizumabSymptomatic radionecrosisEscalation studyOverall survivalPerformance statusResected specimensMulticenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Thomas AA, Abrey LE, Terziev R, Raizer J, Martinez NL, Forsyth P, Paleologos N, Matasar M, Sauter CS, Moskowitz C, Nimer SD, DeAngelis LM, Kaley T, Grimm S, Louis DN, Cairncross JG, Panageas KS, Briggs S, Faivre G, Mohile NA, Mehta J, Jonsson P, Chakravarty D, Gao J, Schultz N, Brennan CW, Huse JT, Omuro A. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma. Neuro-Oncology 2017, 19: 1380-1390. PMID: 28472509, PMCID: PMC5596171, DOI: 10.1093/neuonc/nox086.Peer-Reviewed Original ResearchConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyStem cell transplantAnaplastic oligodendrogliomaAnaplastic oligoastrocytomaHDC-ASCTMulticenter phase II studyMyeloablative high-dose chemotherapyChemotherapy-based approachesCycles of temozolomideOverall survival 93Phase II studyRadiation-related toxicityUnexpected adverse eventsNext-generation sequencingChemotherapy-sensitive tumorsWide molecular heterogeneityToxic deathsAdverse eventsII studyMyeloablative chemotherapyProspective trialIntact patientsCell transplantDynamic contrast‐enhanced MRI perfusion for differentiating between melanoma and lung cancer brain metastases
Hatzoglou V, Tisnado J, Mehta A, Peck KK, Daras M, Omuro AM, Beal K, Holodny AI. Dynamic contrast‐enhanced MRI perfusion for differentiating between melanoma and lung cancer brain metastases. Cancer Medicine 2017, 6: 761-767. PMID: 28303695, PMCID: PMC5387174, DOI: 10.1002/cam4.1046.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesNSCLC brain metastasesLung cancer brain metastasesBrain metastasesCancer brain metastasesCell lung cancer brain metastasesDCE-MRIPrimary brain tumorsDifferent primary sitesImportant clinical implicationsMann-Whitney U testVolume transfer coefficientTumor histologyMultiple malignanciesMRI perfusionBrain tumorsMetastasisPrimary siteConventional MRIClinical implicationsPerfusion parametersTumor microvasculatureROC analysisU testPlasma volume