2023
Multicenter 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
Machine Learning in Differentiating Gliomas from Primary CNS Lymphomas: A Systematic Review, Reporting Quality, and Risk of Bias Assessment
Petersen G, Shatalov J, Verma T, Brim WR, Subramanian H, Brackett A, Bahar RC, Merkaj S, Zeevi T, Staib LH, Cui J, Omuro A, Bronen RA, Malhotra A, Aboian MS. Machine Learning in Differentiating Gliomas from Primary CNS Lymphomas: A Systematic Review, Reporting Quality, and Risk of Bias Assessment. American Journal Of Neuroradiology 2022, 43: 526-533. PMID: 35361577, PMCID: PMC8993193, DOI: 10.3174/ajnr.a7473.Peer-Reviewed Original ResearchConceptsMachine learning-based methodsLearning-based methodsBalanced data setData setsVector machine modelMachine learningClassification algorithmsMachine modelMachineAlgorithmData basesPrediction modelPromising resultsPrimary CNS lymphomaPrediction model study RiskRisk of biasRadiomic featuresClassifierSetCNS lymphomaWebLearningFeaturesQualitySystematic review
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
Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas
Nayak L, de Groot J, Wefel JS, Cloughesy TF, Lieberman F, Chang SM, Omuro A, Drappatz J, Batchelor TT, DeAngelis LM, Gilbert MR, Aldape KD, Yung AW, Fisher J, Ye X, Chen A, Grossman S, Prados M, Wen PY. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas. Journal Of Neuro-Oncology 2017, 132: 181-188. PMID: 28116649, PMCID: PMC5588922, DOI: 10.1007/s11060-016-2357-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingBrain NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyDacarbazineDrug Therapy, CombinationFemaleGliomaHumansMaleMiddle AgedNeuropsychological TestsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsTemozolomideTreatment OutcomeVascular Endothelial Growth Factor AConceptsHigh-grade gliomasPhase I trialI trialArm 2Arm 1Anti-vascular endothelial growth factor therapyAdult Brain Tumor ConsortiumEndothelial growth factor therapyRecombinant human fusion proteinGrowth factorFull treatment courseGrowth factor therapyPlacental growth factorSoluble decoy receptorHuman fusion proteinKPS 90Primary endpointFactor therapyDay regimenMedian ageTreatment courseArm 3Disease progressionMedian numberRadiation therapy
2016
Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
Xu R, Shimizu F, Hovinga K, Beal K, Karimi S, Droms L, Peck KK, Gutin P, Iorgulescu JB, Kaley T, DeAngelis L, Pentsova E, Nolan C, Grommes C, Chan T, Bobrow D, Hormigo A, Cross JR, Wu N, Takebe N, Panageas K, Ivy P, Supko JG, Tabar V, Omuro A. Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial. Clinical Cancer Research 2016, 22: 4786-4796. PMID: 27154916, PMCID: PMC5050072, DOI: 10.1158/1078-0432.ccr-16-0048.Peer-Reviewed Original ResearchConceptsRecurrent tumorsCancer-initiating cell populationGamma secretase inhibitor RO4929097Blood-brain barrier disruptionBlood-brain barrier penetrationDose-limiting toxicityNotch intracellular domainPotential therapeutic optionSignificant decreaseRelative plasma volumeHigh-grade gliomasTumor explant culturesNotch pathwayI trialDismal prognosisTherapeutic optionsBarrier disruptionDrug exposureAnaplastic astrocytomaAngiogenic factorsTumor tissueAntiangiogenic roleTarget modulationDrug penetrationPerfusion MRI
2015
Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma
de la Fuente MI, Young RJ, Rubel J, Rosenblum M, Tisnado J, Briggs S, Arevalo-Perez J, Cross JR, Campos C, Straley K, Zhu D, Dong C, Thomas A, Omuro AA, Nolan CP, Pentsova E, Kaley TJ, Oh JH, Noeske R, Maher E, Choi C, Gutin PH, Holodny AI, Yen K, DeAngelis LM, Mellinghoff IK, Thakur SB. Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. Neuro-Oncology 2015, 18: 283-290. PMID: 26691210, PMCID: PMC4724186, DOI: 10.1093/neuonc/nov307.Peer-Reviewed Original ResearchConceptsTumor volumeDisease monitoringIsocitrate dehydrogenase (IDH) mutant gliomasProton magnetic resonance spectroscopyConsecutive glioma patientsMR imaging protocolMagnetic resonance spectroscopyCytoreductive therapyTumor levelsLarge tumorsTumor gradeSmall tumorsGlioma patientsGlioma imagingGlioma therapyClinical practiceClinical implicationsRoutine MRTumor cellularityTumor cellsIDH-mutant gliomasGliomasMetabolite RImaging protocolMitotic indexA prospective trial of dynamic contrast-enhanced MRI perfusion and fluorine-18 FDG PET-CT in differentiating brain tumor progression from radiation injury after cranial irradiation
Hatzoglou V, Yang TJ, Omuro A, Gavrilovic I, Ulaner G, Rubel J, Schneider T, Woo KM, Zhang Z, Peck KK, Beal K, Young RJ. A prospective trial of dynamic contrast-enhanced MRI perfusion and fluorine-18 FDG PET-CT in differentiating brain tumor progression from radiation injury after cranial irradiation. Neuro-Oncology 2015, 18: 873-880. PMID: 26688076, PMCID: PMC4864262, DOI: 10.1093/neuonc/nov301.Peer-Reviewed Original ResearchConceptsRadiation injuryPET-CTRadiation therapyProspective trialDCE-MRITumor progressionMaximum standardized uptake valueFluorine-18 fluorodeoxyglucose PET-CTFDG PET-CTDiagnosis of progressionNormal brain ratioFluorodeoxyglucose PET-CTStandardized uptake valueDynamic contrast-enhanced MRIWilcoxon rank sum testContrast-enhanced MRIBrain tumor progressionEffective imaging techniqueVolume transfer coefficientRank sum testCranial irradiationBrain ratioBrain malignanciesLesion outcomeBrain lesionsPhase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro-Oncology 2015, 17: 1275-1283. PMID: 26019185, PMCID: PMC4588757, DOI: 10.1093/neuonc/nov083.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasAdverse eventsRadiation therapySkin biopsiesPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyPI3K/mTOR pathway inhibitionTreatment-related gradeDose-escalation studyDose-escalation designFavorable safety profileMTOR pathway inhibitionEvaluable patientsStable diseasePartial responsePharmacodynamic effectsPlatelet countRapamycin inhibitorsSafety profilePreliminary efficacyTumor responsePlasma pharmacokineticsVoxtalisibPatientsGlutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo
Venneti S, Dunphy MP, Zhang H, Pitter KL, Zanzonico P, Campos C, Carlin SD, La Rocca G, Lyashchenko S, Ploessl K, Rohle D, Omuro AM, Cross JR, Brennan CW, Weber WA, Holland EC, Mellinghoff IK, Kung HF, Lewis JS, Thompson CB. Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Science Translational Medicine 2015, 7: 274ra17. PMID: 25673762, PMCID: PMC4431550, DOI: 10.1126/scitranslmed.aaa1009.Peer-Reviewed Original ResearchConceptsPositron emission tomographyPermeable blood-brain barrierChemo/radiation therapyHigh tumor/background ratiosClear tumor delineationDecreased tumor burdenHigh background uptakeTumor/background ratiosBlood-brain barrierAltered glucose metabolismHuman glioma patientsVivo positron emission tomographyProgressive diseaseTumor burdenMetabolic evaluationBrain uptakeClinical managementTumor avidityGlioma patientsRadiation therapyGlucose metabolismBackground uptakeEmission tomographyGliomasCancer cellsDiffusion and Perfusion MRI to Differentiate Treatment-Related Changes Including Pseudoprogression from Recurrent Tumors in High-Grade Gliomas with Histopathologic Evidence
Prager A, Martinez N, Beal K, Omuro A, Zhang Z, Young R. Diffusion and Perfusion MRI to Differentiate Treatment-Related Changes Including Pseudoprogression from Recurrent Tumors in High-Grade Gliomas with Histopathologic Evidence. American Journal Of Neuroradiology 2015, 36: 877-885. PMID: 25593202, PMCID: PMC4731220, DOI: 10.3174/ajnr.a4218.Peer-Reviewed Original ResearchConceptsTreatment-related changesRecurrent tumorsHigh-grade gliomasSurgical resectionRecurrent high-grade gliomaLow relative cerebral blood volumeSubanalysis of patientsUtility of DWIRelative cerebral blood volumeTreatment-related effectsCerebral blood volumeWilcoxon rank sum testConventional MR imagingRank sum testConsecutive patientsHistopathologic evidenceMass lesionDSC perfusionRadiation therapyBlood volumeGrade gliomasPatientsLow perfusionTumorsDSC maps
2012
Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma
Omuro A, Chan TA, Abrey LE, Khasraw M, Reiner AS, Kaley TJ, Deangelis LM, Lassman AB, Nolan CP, Gavrilovic IT, Hormigo A, Salvant C, Heguy A, Kaufman A, Huse JT, Panageas KS, Hottinger AF, Mellinghoff I. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro-Oncology 2012, 15: 242-250. PMID: 23243055, PMCID: PMC3548585, DOI: 10.1093/neuonc/nos295.Peer-Reviewed Original ResearchConceptsKarnofsky performance scoreProgression-free survival ratesBevacizumab-naive patientsRecurrent malignant gliomaPhase II trialMalignant gliomasII trialPrimary endpointSurvival rateContinuous low-dose temozolomideMedian Karnofsky performance scoreLow Karnofsky performance scoreAdvanced malignant gliomaLow-dose temozolomideMedian overall survivalHalf of patientsFurther treatment strategiesMutations of EGFRBevacizumab exposureEligible patientsTemozolomide schedulesMG patientsOverall survivalMedian ageClinical benefit
2011
Continuing the search for MR imaging biomarkers for MGMT promoter methylation status: conventional and perfusion MRI revisited
Gupta A, Omuro AM, Shah AD, Graber JJ, Shi W, Zhang Z, Young RJ. Continuing the search for MR imaging biomarkers for MGMT promoter methylation status: conventional and perfusion MRI revisited. Neuroradiology 2011, 54: 641-643. PMID: 22006425, PMCID: PMC4724213, DOI: 10.1007/s00234-011-0970-z.Peer-Reviewed Original Research
2010
Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide
Kaloshi G, Sierra del Rio M, Ducray F, Psimaras D, Idbaih A, Laigle-Donadey F, Taillibert S, Houillier C, Dehais C, Omuro A, Sanson M, Delattre JY, Hoang-Xuan K. Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide. Journal Of Neuro-Oncology 2010, 100: 439-441. PMID: 20464625, DOI: 10.1007/s11060-010-0197-6.Peer-Reviewed Original ResearchConceptsLow-grade gliomasGrade gliomasProgressive low-grade gliomaTerms of PFSContrast enhancementEfficacy of nitrosoureasBetter PFSMedian PFSMedian OSObjective responseSalvage treatmentUpfront therapyMedian ageBetter prognosisInitial treatmentConventional radiotherapyChromosome 1p/19q codeletionNon-enhancing tumorResponse ratePatientsTemozolomidePure oligodendrogliomasPFSGliomasDisappointing results
2008
What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas?
Omuro AM, Delattre JY. What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas? Current Opinion In Neurology 2008, 21: 717-719. PMID: 18989118, DOI: 10.1097/wco.0b013e3283184625.Peer-Reviewed Original ResearchConceptsMalignant gliomasOverall survivalClinical trialsProspective phase II trialPlace of bevacizumabProgression-free survivalPhase II trialNew treatment strategiesHigh response rateTreatment of glioblastomaII trialRecurrent diseaseSalvage treatmentCytotoxic chemotherapyMost patientsConventional radiographic methodsDisease progressionHistorical controlsSurvival resultsRadiographic criteriaTreatment strategiesBevacizumabResponse rateNew treatmentsGliomas
2007
Editorial: what is new in the treatment of gliomas?
Omuro AM, Delattre JY. Editorial: what is new in the treatment of gliomas? Current Opinion In Neurology 2007, 20: 704-707. PMID: 17992093, DOI: 10.1097/wco.0b013e3282f1beef.Peer-Reviewed Original ResearchConceptsTreatment of gliomaTherapeutic decisionsEvidence-based therapeutic decisionsBevacizumab-based combinationsRecurrent malignant gliomaRole of chemotherapyPhase II trialStandard of carePhase III evidenceHigh response ratePhase II resultsSingle positive resultTemozolomide concomitantTemozolomide schedulesII trialSurvival benefitRandomized trialsGrade IIIMalignant gliomasResponse rateGliomasSuch trialsTraditional treatmentTrialsCodeletion statusMolecular genetic markers as predictors of response to chemotherapy in gliomas
Idbaih A, Omuro A, Ducray F, Hoang-Xuan K. Molecular genetic markers as predictors of response to chemotherapy in gliomas. Current Opinion In Oncology 2007, 19: 606-611. PMID: 17906460, DOI: 10.1097/cco.0b013e3282f075f3.Peer-Reviewed Original ResearchConceptsAnaplastic oligodendroglial tumorsLow-grade gliomasProspective trialMGMT statusOligodendroglial tumorsIndependent favorable prognostic factorFavorable prognostic factorRelevant prognostic markerPredictors of responsePromoter methylationTreatment of gliomaPredictor of chemosensitivityMGMT promoter methylationObjective responsePrognostic factorsRetrospective studyPrognostic markerSuch tumorsTreatment decisionsChromosome 1p/19q codeletionMGMT inactivationPredictive valueChemotherapyGliomasLow expressionLessons learned in the development of targeted therapy for malignant gliomas
Omuro AM, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Molecular Cancer Therapeutics 2007, 6: 1909-1919. PMID: 17620423, DOI: 10.1158/1535-7163.mct-07-0047.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor receptorEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsPreliminary efficacy resultsPrognosis of patientsTranslational researchEndothelial growth factor receptorEffective treatment optionTyrosine kinase inhibitorsGrowth factor receptorRecurrent diseaseRapamycin inhibitorsPreclinical dataStandard treatmentTreatment optionsEfficacy resultsMalignant gliomasSuch tumorsNovel agentsAnaplastic astrocytomaMost trialsTrial designProtein kinase C betaPathway inhibitorTemozolomide for low-grade gliomas
Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, Renard M, Iraqi W, Idbaih A, Paris S, Capelle L, Duffau H, Cornu P, Simon J, Mokhtari K, Polivka M, Omuro A, Carpentier A, Sanson M, Delattre J, Hoang-Xuan K. Temozolomide for low-grade gliomas. Neurology 2007, 68: 1831-1836. PMID: 17515545, DOI: 10.1212/01.wnl.0000262034.26310.a2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingBrain NeoplasmsChromosome DeletionChromosomes, Human, Pair 1Chromosomes, Human, Pair 19DacarbazineDNA Mutational AnalysisDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGenetic TestingGenotypeGliomaHumansLoss of HeterozygosityMaleMiddle AgedNeoplasm Recurrence, LocalRetrospective StudiesSurvival RateTemozolomideTreatment OutcomeConceptsProgression-free survivalLow-grade gliomasProgressive low-grade gliomaObjective responseMedian progression-free survivalLonger progression-free survivalSingle-center observational studyCenter observational studyMaximum tumor responseStable diseaseProgressive diseaseAdult patientsConsecutive patientsOverall survivalMedian timeTMZ cyclesTemozolomide chemotherapyCentral reviewTumor responseFavorable outcomeMedian numberObservational studyPatientsPredictive impactConventional scheduleDynamic history of low‐grade gliomas before and after temozolomide treatment
Ricard D, Kaloshi G, Amiel‐Benouaich A, Lejeune J, Marie Y, Mandonnet E, Kujas M, Mokhtari K, Taillibert S, Laigle‐Donadey F, Carpentier AF, Omuro A, Capelle L, Duffau H, Cornu P, Guillevin R, Sanson M, Hoang‐Xuan K, Delattre J. Dynamic history of low‐grade gliomas before and after temozolomide treatment. Annals Of Neurology 2007, 61: 484-490. PMID: 17469128, DOI: 10.1002/ana.21125.Peer-Reviewed Original ResearchConceptsMean tumor diameterLow-grade gliomasMajority of tumorsTemozolomide treatmentImpact of temozolomideSerial magnetic resonance imagesUntreated low-grade gliomaGenetic alterationsNeoadjuvant temozolomideTumor diameterContinuous administrationP53 overexpressionOptimal durationTumor progressionTumorsTemozolomidePatientsGliomasMagnetic resonance imagesNatural progressionTreatmentProgressive growthLower ratesResonance imagesP53