2024
Radiotherapy Plan Quality Assurance in NRG Oncology Trials for Brain and Head/Neck Cancers: An AI-Enhanced Knowledge-Based Approach
Wang D, Geng H, Gondi V, Lee N, Tsien C, Xia P, Chenevert T, Michalski J, Gilbert M, Le Q, Omuro A, Men K, Aldape K, Cao Y, Srinivasan A, Barani I, Sachdev S, Huang J, Choi S, Shi W, Battiste J, Wardak Z, Chan M, Mehta M, Xiao Y. Radiotherapy Plan Quality Assurance in NRG Oncology Trials for Brain and Head/Neck Cancers: An AI-Enhanced Knowledge-Based Approach. Cancers 2024, 16: 2007. PMID: 38893130, PMCID: PMC11171017, DOI: 10.3390/cancers16112007.Peer-Reviewed Original ResearchIntensity-modulated proton therapyPlan quality assuranceOrgan-at-riskRT planningQuality of radiation therapyClinical trialsIMPT plansKBP modelPlan QAPhoton plansRadiation therapyPhoton modelKBP plansTarget coveragePlan qualityProton therapyNasopharyngeal carcinomaMulti-institutional clinical trialsNRG Oncology trialsProton modelOutcomes of clinical trialsMulti-center clinical trialPhoton RTQuality assuranceHead/neck cancer
2023
CTNI-41. PHASE II AND PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS
Schiff D, Bindra R, Li J, Ye X, Ellingson B, Walbert T, Campian J, Nabors B, Lieberman F, Ozer B, Desai A, Omuro A, Wen P, Desideri S, Danda N, Grossman S. CTNI-41. PHASE II AND PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS. Neuro-Oncology 2023, 25: v84-v84. PMCID: PMC10639307, DOI: 10.1093/neuonc/noad179.0323.Peer-Reviewed Original ResearchObjective response rateArm AMetronomic temozolomideArm BGrade 3Non-enhancing tumorMeaningful objective response rateTumor/plasma ratioCumulative hematologic toxicityGrade 3 anemiaGrade 3 thrombocytopeniaGrade 4 neutropeniaPhase II componentArm clinical trialPhase IIKPS 90Median PFSHematologic toxicityPrimary endpointAlkylator therapyProgressive diseaseARM patientsMedian ageBRCAness phenotypeClinical trials
2022
Immune-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 dysfunction
2021
CTNI-18. PHASE I AND PRELIMINARY PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB (BGB290) WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS
Schiff D, Bindra R, Li J, Ye X, Ellingson B, Walbert T, Campian J, Nabors L, Lieberman F, Ozer B, Desai A, Omuro A, Wen P, Desideri S, Fisher J, Grossman S. CTNI-18. PHASE I AND PRELIMINARY PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB (BGB290) WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS. Neuro-Oncology 2021, 23: vi63-vi63. DOI: 10.1093/neuonc/noab196.243.Peer-Reviewed Original ResearchMetronomic temozolomidePhase IFavorable brain penetrationDose level 1Phase II studyGrade 2 neutropeniaArm clinical trialKPS 90Inadequate dosingPrior radiotherapyAlkylator therapyHematological toxicityII studyMedian ageAdditional patientsStudy treatmentBrain penetrationRelapse 3BRCAness phenotypeClinical trialsIDH1 mutant gliomasSurgical armTemozolomide dosePreclinical studiesAnaplastic astrocytoma
2020
Evaluation of Photon and Proton Radiotherapy Plan Quality With the Knowledge-Based Approach in NRG BN001 Clinical Trial
Wang D, Gondi V, Tsien C, Chenevert T, Gilbert M, Omuro A, McDonough J, Aldape K, Cao Y, Srinivasan A, Rogers L, Grimm S, Huang J, Machtay M, Martinez N, Bahary J, Nedzi L, Mehta M, Xiao Y. Evaluation of Photon and Proton Radiotherapy Plan Quality With the Knowledge-Based Approach in NRG BN001 Clinical Trial. International Journal Of Radiation Oncology • Biology • Physics 2020, 108: e344-e345. DOI: 10.1016/j.ijrobp.2020.07.822.Peer-Reviewed Original ResearchA 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 profile
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 teamMetastasisPatients
2017
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Grommes C, Pastore A, Palaskas N, Tang SS, Campos C, Schartz D, Codega P, Nichol D, Clark O, Hsieh WY, Rohle D, Rosenblum M, Viale A, Tabar VS, Brennan CW, Gavrilovic IT, Kaley TJ, Nolan CP, Omuro A, Pentsova E, Thomas AA, Tsyvkin E, Noy A, Palomba ML, Hamlin P, Sauter CS, Moskowitz CH, Wolfe J, Dogan A, Won M, Glass J, Peak S, Lallana EC, Hatzoglou V, Reiner AS, Gutin PH, Huse JT, Panageas KS, Graeber TG, Schultz N, DeAngelis LM, Mellinghoff IK. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discovery 2017, 7: 1018-1029. PMID: 28619981, PMCID: PMC5581705, DOI: 10.1158/2159-8290.cd-17-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntineoplastic AgentsCARD Signaling Adaptor ProteinsCentral Nervous System NeoplasmsDrug Resistance, NeoplasmFemaleGuanylate CyclaseHumansLymphoma, B-CellMaleMaximum Tolerated DoseMiddle AgedMutationPiperidinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinesTreatment OutcomeYoung AdultConceptsPrimary central nervous system lymphomaBruton's tyrosine kinaseB-cell lymphomaRefractory B-cell lymphomaB cell antigen receptorCentral nervous system lymphomaRole of BTKDiffuse large B-cell lymphomaLarge B-cell lymphomaPhase I clinical trialClass BTK inhibitorIncomplete tumor responseNervous system lymphomaToll-like receptorsPI3K/mTORIbrutinib responseCNS lymphomaClinical responseComplete responseReceptor-associated proteinSystem lymphomaActivation markersTumor responseClinical trialsPCNSL cellsPhase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Tun H, Johnston P, Grommes C, Reeder C, Omuro A, Menke D, Copland J, DeAngelis L, Witzig T. Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL). Journal Of Clinical Oncology 2017, 35: 7516-7516. DOI: 10.1200/jco.2017.35.15_suppl.7516.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaOverall response rateRefractory primary central nervous system lymphomaPhase I clinical trialPrimary vitreoretinal lymphomaMTD cohortStable diseaseClinical trialsCentral nervous system lymphomaTherapeutic activityDiffuse large B-cell lymphomaLarge B-cell lymphomaDose level 3Grade 3/4 toxicitiesNovel immunomodulatory agentsNervous system lymphomaCycles of treatmentDose escalation levelsCSF/blood ratioB-cell lymphomaExcellent CNS penetrationPO weeklyPomalidomide treatmentPseudo progressionCNS lymphomaMutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, Srinivasan P, Gao J, Chakravarty D, Devlin SM, Hellmann MD, Barron DA, Schram AM, Hameed M, Dogan S, Ross DS, Hechtman JF, DeLair DF, Yao J, Mandelker DL, Cheng DT, Chandramohan R, Mohanty AS, Ptashkin RN, Jayakumaran G, Prasad M, Syed MH, Rema AB, Liu ZY, Nafa K, Borsu L, Sadowska J, Casanova J, Bacares R, Kiecka IJ, Razumova A, Son JB, Stewart L, Baldi T, Mullaney KA, Al-Ahmadie H, Vakiani E, Abeshouse AA, Penson AV, Jonsson P, Camacho N, Chang MT, Won HH, Gross BE, Kundra R, Heins ZJ, Chen HW, Phillips S, Zhang H, Wang J, Ochoa A, Wills J, Eubank M, Thomas SB, Gardos SM, Reales DN, Galle J, Durany R, Cambria R, Abida W, Cercek A, Feldman DR, Gounder MM, Hakimi AA, Harding JJ, Iyer G, Janjigian YY, Jordan EJ, Kelly CM, Lowery MA, Morris LGT, Omuro AM, Raj N, Razavi P, Shoushtari AN, Shukla N, Soumerai TE, Varghese AM, Yaeger R, Coleman J, Bochner B, Riely GJ, Saltz LB, Scher HI, Sabbatini PJ, Robson ME, Klimstra DS, Taylor BS, Baselga J, Schultz N, Hyman DM, Arcila ME, Solit DB, Ladanyi M, Berger MF. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nature Medicine 2017, 23: 703-713. PMID: 28481359, PMCID: PMC5461196, DOI: 10.1038/nm.4333.Peer-Reviewed Original ResearchConceptsMemorial Sloan-Kettering Cancer CenterCancer-related genesProspective clinical sequencingAdvanced solid cancersSequencing platformsStructural variantsGenomic landscapeGenomic mutationsDetailed clinical annotationMutational landscapeSequencing resultsNumber alterationsCancer CenterPatient enrollmentClinical trialsMSK-IMPACTMetastatic cancerSolid cancersNew insightsNormal tissuesClinical sequencingCancer therapyPatientsCancerClinical annotation
2014
Emerging Therapies for Glioblastoma
Thomas AA, Brennan CW, DeAngelis LM, Omuro AM. Emerging Therapies for Glioblastoma. JAMA Neurology 2014, 71: 1437-1444. PMID: 25244650, DOI: 10.1001/jamaneurol.2014.1701.Peer-Reviewed Original ResearchConceptsClinical trialsCommon primary malignant brain tumorPrimary malignant brain tumorCancer stemlike cellsInnovative clinical trialsBlood-brain barrierMalignant brain tumorsPatient-tailored treatmentNew radiotherapy techniquesHeterogeneous molecular featuresImmune system interactionsGrowth factor receptorTerms glioblastomaMedian survivalDisease courseImmune checkpointsTemozolomide chemotherapyMultimodal treatmentPatient enrollmentAggressive tumorsTreatment advancesBrain neoplasmsDrug exposureBrain microenvironmentMalignant gliomasAT-07A PHASE II STUDY OF LAPATINIB AND DOSE-DENSE TEMOZOLOMIDE (TMZ) FOR ADULTS WITH RECURRENT EPENDYMOMA: PATIENT REPORTED OUTCOMES (PRO) FROM A CERN CLINICAL TRIAL
Armstrong T, Vera-Bolanos E, Gilbert M, Yuan Y, Wani K, Wu J, Omuro A, Lieberman F, Robins H, Gerstner E, Wu J, Wen P, Mikkelsen T, Aldape K, Mendoza T. AT-07A PHASE II STUDY OF LAPATINIB AND DOSE-DENSE TEMOZOLOMIDE (TMZ) FOR ADULTS WITH RECURRENT EPENDYMOMA: PATIENT REPORTED OUTCOMES (PRO) FROM A CERN CLINICAL TRIAL. Neuro-Oncology 2014, 16: v9-v9. PMCID: PMC4217844, DOI: 10.1093/neuonc/nou237.7.Peer-Reviewed Original ResearchDose-dense temozolomideProgression-free survivalSymptom burdenClinical trialsDisease progressionRecurrent ependymomaFirst prospective clinical trialMedian progression-free survivalPatient Reported Outcome MeasuresPhase II studyOverall symptom burdenProspective clinical trialsPrimary CNS tumorCycle 6Majority of symptomsDry mouthFree survivalPrimary endpointRecurrent diseaseSymptom benefitCNS tumorII studyTreatment courseSymptom interferenceVision changesAT-47PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES
Raizer J, Pentsova E, Omuro A, Lin N, Nayak L, Quant E, Kumthekar P. AT-47PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES. Neuro-Oncology 2014, 16: v19-v19. PMCID: PMC4217826, DOI: 10.1093/neuonc/nou237.46.Peer-Reviewed Original ResearchHER2-positive breast cancerPositive breast cancerLeptomeningeal metastasesDose levelsBreast cancerIntrathecal trastuzumabCentral nervous system penetrationPhase I clinical trialPhase II studyHumanized monoclonal antibodyIT trastuzumabMedian KPSII studyProgressive diseaseI trialMedian ageOmmaya reservoirCSF levelsAnaplastic ependymomaClinical trialsPatientsPK dataTherapeutic levelsIts TreatmentTrastuzumabAT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL
Lassman A, Grommes C, Panageas K, Iwamoto F, DeAngelis L, Kaley T, Gavrilovic I, Pentsova E, Omuro A, Corpuz C, Briggs S, Otap D, Qin W, Cross J, Mellinghoff I. AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL. Neuro-Oncology 2014, 16: v16-v16. PMCID: PMC4217814, DOI: 10.1093/neuonc/nou237.35.Peer-Reviewed Original ResearchRecurrent malignant gliomaMalignant gliomasInhibitor therapyHigh-dose erlotinibOngoing complete responseEGFR-TKI erlotinibPopulation of patientsMedian age 58Pilot clinical trialInadequate drug deliveryKinase inhibitor therapyDose erlotinibEligible patientsPulsatile dosingAdverse eventsMedian survivalComplete responseDaily doseTKI erlotinibMedian CmaxAnaplastic gliomasClinical trialsAge 58Surgical armLimited efficacyAT-23A PHASE II STUDY OF LAPATINIB AND DOSE-DENSE TEMOZOLOMIDE (TMZ) FOR ADULTS WITH RECURRENT EPENDYMOMA: A CERN CLINICAL TRIAL
Gilbert M, Yuan Y, Wani K, Wu J, Omuro A, Lieberman F, Robins H, Gerstner E, Wu J, Wen P, Mikkelsen T, Armstrong T, Aldape K. AT-23A PHASE II STUDY OF LAPATINIB AND DOSE-DENSE TEMOZOLOMIDE (TMZ) FOR ADULTS WITH RECURRENT EPENDYMOMA: A CERN CLINICAL TRIAL. Neuro-Oncology 2014, 16: v13-v13. PMCID: PMC4217801, DOI: 10.1093/neuonc/nou237.23.Peer-Reviewed Original ResearchDose-dense temozolomideClinical trialsPredictive markerFirst prospective clinical trialPhase II studyPrimary CNS tumorsProspective clinical trialsPossible predictive markerPotential predictive markerPatient reported outcomesSubsequent clinical trialsMGMT promoter statusMedian KPSMedian progressionPrimary endpointRecurrent diseaseII studyOverall survivalSymptom burdenMedian ageInitial treatmentCNS tumorsExtensive resectionStandard treatmentPRO collection
2011
Pharmacotherapy for Primary CNS Lymphoma
Graber JJ, Omuro A. Pharmacotherapy for Primary CNS Lymphoma. CNS Drugs 2011, 25: 447-457. PMID: 21649446, DOI: 10.2165/11589030-000000000-00000.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaCNS lymphomaHigh-dose methotrexate-based chemotherapyMore effective chemotherapy regimensRefractory primary CNS lymphomaEffective chemotherapy regimensOptimal chemotherapy combinationReduced-dose radiotherapySingle-agent methotrexateMethotrexate-based chemotherapyStem cell rescueWhole brain radiotherapyHigh-dose chemotherapyLong-term remissionProgression-free survivalOngoing clinical trialsCombination of drugsChemotherapy regimensChemotherapy combinationsChemotherapy optionsRadiotherapy resultsSerious complicationsClinical trialsCell rescueConsolidation treatment
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