2024
ONC201 (Dordaviprone) in Recurrent H3 K27M–Mutant Diffuse Midline Glioma
Arrillaga-Romany I, Gardner S, Odia Y, Aguilera D, Allen J, Batchelor T, Butowski N, Chen C, Cloughesy T, Cluster A, de Groot J, Dixit K, Graber J, Haggiagi A, Harrison R, Kheradpour A, Kilburn L, Kurz S, Lu G, MacDonald T, Mehta M, Melemed A, Nghiemphu P, Ramage S, Shonka N, Sumrall A, Tarapore R, Taylor L, Umemura Y, Wen P. ONC201 (Dordaviprone) in Recurrent H3 K27M–Mutant Diffuse Midline Glioma. Journal Of Clinical Oncology 2024, 42: 1542-1552. PMID: 38335473, PMCID: PMC11095894, DOI: 10.1200/jco.23.01134.Peer-Reviewed Original ResearchConceptsH3 K27M-mutant diffuse midline gliomaDiffuse midline gliomaDuration of responseTime to responseHigh-grade gliomasLow-grade gliomasMidline gliomaMedian duration of responseMedian time to responseTreatment-emergent adverse eventsEnd pointsBlinded independent central reviewCorticosteroid dose reductionIndependent central reviewSecondary end pointsClinically meaningful efficacyRadiographic end pointsSpinal tumorsDose reductionDismal prognosisCentral reviewPerformance scoresCorticosteroid responseResponse assessmentAdverse events
2023
Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma.
Kurz S, Zan E, Cordova C, Troxel A, Barbaro M, Silverman J, Snuderl M, Zagzag D, Kondziolka D, Golfinos J, Chi A, Sulman E. Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma. Clinical Cancer Research 2023, 30: 680-686. PMID: 38048045, DOI: 10.1158/1078-0432.ccr-23-2533.Peer-Reviewed Original ResearchConceptsProgression-free survivalSomatostatin receptor type 2PFS-6Stable diseaseOverall survivalIntracranial meningiomasSingle-arm phase II clinical studyMedian progression-free survivalPhase II clinical studyImaging biomarkersCourse of radiationReceptor type 2Multicenter clinical trialMacdonald criteriaMedian OSRadiographic responseProgressive meningiomasTumor measurementsTumor resectionMedian agePrimary endpointRadiotherapeutic interventionSecondary endpointsMedical therapyAdult patientsTowards more Diversity in Neuro-oncology Leadership—the DivINe Initiative
Kurz S, Stammberger A, Rosahl S, Abrey L, Albert N, von Baumgarten L, Gempt J, Grosu A, Leidgens V, McLean A, Renovanz M, Schwarzenberger J, Sevenich L, Purkart T, Combs S, Tabatabai G, Hegi M, Nowosielski M. Towards more Diversity in Neuro-oncology Leadership—the DivINe Initiative. Neuro-Oncology 2023, 25: 2302-2304. PMID: 37738478, PMCID: PMC10708925, DOI: 10.1093/neuonc/noad157.Peer-Reviewed Original ResearchAssociation of MTHFR Polymorphisms With Leukoencephalopathy Risk in Patients With Primary CNS Lymphoma Treated With Methotrexate-Based Regimens
Karschnia P, Kurz S, Brastianos P, Winter S, Gordon A, Jones S, Pisapia M, Nayyar N, Tonn J, Batchelor T, Plotkin S, Dietrich J. Association of MTHFR Polymorphisms With Leukoencephalopathy Risk in Patients With Primary CNS Lymphoma Treated With Methotrexate-Based Regimens. Neurology 2023, 101: e1741-e1746. PMID: 37527941, PMCID: PMC10624483, DOI: 10.1212/wnl.0000000000207670.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaCNS lymphomaHD-MTXMethylenetetrahydrofolate reductaseResponse to induction therapyAssociation of MTHFR polymorphismsMethotrexate-based regimensSeverity of leukoencephalopathyProgression-free survivalHigh-dose methotrexateRisk of leukoencephalopathyAssociated with increased frequencyAssociated with leukoencephalopathyInduction chemotherapyDecreased functional statusInduction therapyOverall survivalMassachusetts General HospitalMTX clearanceMTHFR polymorphismsFolate depletionLeukoencephalopathyPatientsElevated riskFunctional status
2022
Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data From Patients With KRASG12C-Mutant Non-Small Cell Lung CancerPreliminary Activity of Adagrasib in Brain Metastases
Sabari J, Velcheti V, Shimizu K, Strickland M, Heist R, Singh M, Nayyar N, Giobbie-Hurder A, Digumarthy S, Gainor J, Rajan A, Nieblas-Bedolla E, Burns A, Hallin J, Olson P, Christensen J, Kurz S, Brastianos P, Wakimoto H. Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data From Patients With KRASG12C-Mutant Non-Small Cell Lung CancerPreliminary Activity of Adagrasib in Brain Metastases. Clinical Cancer Research 2022, 28: 3318-3328. PMID: 35404402, PMCID: PMC9662862, DOI: 10.1158/1078-0432.ccr-22-0383.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerKRAS-mutant non-small cell lung cancerBrain metastasesCerebrospinal fluidAntitumor activityUntreated BMCentral nervous system penetrationDose-dependent pharmacokineticsCell lung cancerKRASG12C inhibitorsPreliminary clinical dataRetrospective database queryCerebrospinal fluid concentrationsPharmacokinetic propertiesExtensive tissue distributionTumor regressionNSCLC xenograftsPreclinical modelsPoor prognosisPreclinical studiesAdagrasibExtended survivalLung cancerClinical dataLong half-life
2021
Functional connectivity of the default mode, dorsal attention and fronto-parietal executive control networks in glial tumor patients
Tordjman M, Madelin G, Gupta P, Cordova C, Kurz S, Orringer D, Golfinos J, Kondziolka D, Ge Y, Wang R, Lazar M, Jain R. Functional connectivity of the default mode, dorsal attention and fronto-parietal executive control networks in glial tumor patients. Journal Of Neuro-Oncology 2021, 152: 347-355. PMID: 33528739, PMCID: PMC8204932, DOI: 10.1007/s11060-021-03706-w.Peer-Reviewed Original ResearchConceptsSeed-based connectivity analysisFronto-parietal networkDefault mode networkHigh-grade gliomasFunctional connectivityFronto-parietal executive control networkGlioma patientsIncreased connectivityFunctional magnetic resonance imagingCorpus callosumDisruption of functional connectivityExecutive control networkPosterior cingulate gyrusPosterior corpus callosumMagnetic resonance imagingResults35 patientsDMN connectivityFrontal cortexMode networkCingulate gyrusDorsal attentionGlial tumorsTumor patientsDecreased connectivityIDH1-R132H
2020
Advances in Molecular Classification and Therapeutic Opportunities in Meningiomas
Cordova C, Kurz S. Advances in Molecular Classification and Therapeutic Opportunities in Meningiomas. Current Oncology Reports 2020, 22: 84. PMID: 32617743, DOI: 10.1007/s11912-020-00937-4.Peer-Reviewed Original ResearchConceptsWHO classification of CNS tumorsClassification of CNS tumorsWHO classificationCNS tumorsWHO grade IDNA methylation patternsBiology of meningiomasClinical trial designPrognostic implicationsTERT promoterTumor biologyGrade IMethylation patternsHistopathological featuresGenetic alterationsEffective therapyLoss of functionMeningiomasMolecular classificationReviewOur understandingDMD geneEpigenetic alterationsTumorEpigenetic changesTherapeutic opportunitiesRacial and socioeconomic disparities differentially affect overall and cause-specific survival in glioblastoma
Liu E, Yu S, Sulman E, Kurz S. Racial and socioeconomic disparities differentially affect overall and cause-specific survival in glioblastoma. Journal Of Neuro-Oncology 2020, 149: 55-64. PMID: 32617722, DOI: 10.1007/s11060-020-03572-y.Peer-Reviewed Original ResearchConceptsCause-specific mortalityMedian household incomeNational Cancer Institute's SurveillanceHousehold incomeCalendar year of diagnosisAssociated with all-cause mortalityNon-Hispanic whitesMethodsThe National Cancer Institute’s SurveillanceAll-cause mortalityCox proportional hazards modelsYear of diagnosisSocioeconomic disparitiesProportional hazards modelAsian/Pacific IslanderInstitute's SurveillanceHispanic whitesSocioeconomic groupsTreatment receiptPatient raceNon-glioblastomaCohort dataSocioeconomic factorsCause-specific mannerInclusion criteriaBlack raceNovel Therapies for Glioblastoma
Liu E, Sulman E, Wen P, Kurz S. Novel Therapies for Glioblastoma. Current Neurology And Neuroscience Reports 2020, 20: 19. PMID: 32445058, DOI: 10.1007/s11910-020-01042-6.Peer-Reviewed Original ResearchConceptsClinical studiesEarly phase clinical studiesNovel radiotherapy approachesSignificant survival benefitMalignant primary brain tumorPhase clinical studiesPersonalized treatment approachesDiverse resistance mechanismsPrimary brain tumorCheckpoint inhibitionRadiotherapy optionsRadiotherapy approachesDose deliveryRadiation modalitiesSurvival benefitBiomarker-drivenTargeted therapyTargeted agentsTreatment optionsNovel therapiesTumor heterogeneityClinical investigationVaccination strategiesBrain tumorsTreatment approaches
2019
Cell Surface Notch Ligand DLL3 is a Therapeutic Target in Isocitrate Dehydrogenase–mutant Glioma
Spino M, Kurz S, Chiriboga L, Serrano J, Zeck B, Sen N, Patel S, Shen G, Vasudevaraja V, Tsirigos A, Suryadevara C, Frenster J, Tateishi K, Wakimoto H, Jain R, Riina H, Nicolaides T, Sulman E, Cahill D, Golfinos J, Isse K, Saunders L, Zagzag D, Placantonakis D, Snuderl M, S. A. Cell Surface Notch Ligand DLL3 is a Therapeutic Target in Isocitrate Dehydrogenase–mutant Glioma. Clinical Cancer Research 2019, 25: 1261-1271. PMID: 30397180, PMCID: PMC7365589, DOI: 10.1158/1078-0432.ccr-18-2312.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedBenzodiazepinonesBrainDNA MethylationFemaleGene Expression Regulation, NeoplasticGenotypeGliomaHumansImmunoconjugatesIntracellular Signaling Peptides and ProteinsIsocitrate DehydrogenaseLigandsMaleMembrane ProteinsMolecular Targeted TherapyMutationNeoplasm Recurrence, LocalReceptors, NotchRNAConceptsGlioma molecular subtypesAntibody-drug conjugatesMolecular subtypesCell surface tumor-associated antigensTumor-associated antigensWild-type glioblastomaAntigen-dependent mannerLow-grade gliomasRova-TRecurrent tumorsDLL3 expressionRovalpituzumab tesirineNontumor brain tissuesNontumor brainMutant gliomasTherapeutic strategiesCell viability assayGliomaRNA levelsDLL3TumorspheresTherapeutic targetIHCTCGA dataWild-type
2018
PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma.
Kurz S, Cabrera L, Hastie D, Huang R, Unadkat P, Rinne M, Nayak L, Lee E, Reardon D, Wen P. PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma. Neurology 2018, 91: e1355-e1359. PMID: 30171077, DOI: 10.1212/wnl.0000000000006283.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBevacizumabBrain NeoplasmsFemaleGliomaHumansMaleMiddle AgedNeoplasm Recurrence, LocalNivolumabProgrammed Cell Death 1 ReceptorRetrospective StudiesSalvage TherapySurvival AnalysisTreatment OutcomeYoung AdultConceptsRecurrent high-grade gliomaHigh-grade gliomasRetrospective observational studySalvage therapySurvival benefitSingle-institution retrospective observational studyPD-1 blocking antibodiesObservational studyPD-1 inhibitionProgression-free survivalClass IV evidenceConcurrent bevacizumabAntibody nivolumabPD-1Median survivalClinical benefitImproved survivalNivolumabPembrolizumabAdult patientsBevacizumabIV evidenceClinical trialsPatient populationPatients