2023
BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structures
2022
Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma.
Fanucci K, Pilat M, Shah R, Boerner S, Li J, Durecki D, Drappatz J, Collichio F, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Bao X, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. Journal Of Clinical Oncology 2022, 40: 2035-2035. DOI: 10.1200/jco.2022.40.16_suppl.2035.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalStable diseaseDuration of responseOverall response ratePARP inhibitorsOverall survivalStandard therapyOlaparib monotherapyMulticenter phase 2 trialCDKN2A deletionClinical predictive markersGrade 3 lymphopeniaProlonged stable diseasePhase 2 trialGrade 4 tumorsFuture patient stratificationRecent preclinical studiesHigh-grade gliomasNovel drug combinationsContrast-enhancing gliomasEligible ptsEvaluable ptsRecent histologyPrimary endpoint
2017
Multicenter, 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 specimensPhase 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
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
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 pharmacokineticsVoxtalisibPatientsDiffusion 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
2014
AI-09PATTERNS OF SALVAGE TREATMENT FOR HIGH GRADE GLIOMA IN THE TEMOZOLOMIDE ERA
Escorcia F, Folkert M, Spratt D, Zumsteg Z, Chan T, Omuro A, Beal K, Gutin P, Yamada J. AI-09PATTERNS OF SALVAGE TREATMENT FOR HIGH GRADE GLIOMA IN THE TEMOZOLOMIDE ERA. Neuro-Oncology 2014, 16: v3-v3. PMCID: PMC4217875, DOI: 10.1093/neuonc/nou238.9.Peer-Reviewed Original ResearchHigh-grade gliomasSalvage radiation therapyTreatment-related factorsTrimodality therapyRadiation therapySalvage chemotherapyHazard ratioOverall survivalGrade gliomasOnly treatment-related factorOptimal salvage therapyKaplan-Meier methodCox regression modelingGrade IV patientsLarge retrospective seriesConfidence intervalsSalvage therapyTrimodality treatmentBilateral diseaseInitial surgeryRecurrent diseaseSalvage surgerySalvage treatmentIV patientsConsecutive patients