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 patientsAssociation 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 statusMTHFR polymorphisms and neurotoxicity and overall survival after methotrexate-based therapy in primary CNS lymphoma.
Karschnia P, Kurz S, Brastianos P, Winter S, Gordon A, Jones S, Pisapia M, Nayyar N, Tonn J, Batchelor T, Plotkin S, Dietrich J. MTHFR polymorphisms and neurotoxicity and overall survival after methotrexate-based therapy in primary CNS lymphoma. Journal Of Clinical Oncology 2023, 41: 2079-2079. DOI: 10.1200/jco.2023.41.16_suppl.2079.Peer-Reviewed Original ResearchPrimary CNS lymphomaMethylenetetrahydrofolate reductase polymorphismPrimary CNS lymphoma patientsHD-MTXMethylenetetrahydrofolate reductaseOverall survivalC genotypeCNS lymphomaPatients treated with HD-MTXEffect of HD-MTXHD-MTX-based therapyAssociated with reduced overall survivalAssociation of MTHFR polymorphismsSeverity of leukoencephalopathyKaplan-Meier survival analysisProgression-free survivalLog-rank testMethylenetetrahydrofolate reductase genotypeAssociated with increased frequencyIntracellular folate metabolismAssociated with toxicityCerebral white matterInduction chemotherapyDecreased functional statusMassachusetts General Hospital
2022
CTNI-57. RADIONUCLIDE THERAPY WITH 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA - INTERIM ANALYSIS RESULTS OF A SINGLE-ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY
Kurz S, Zan E, Cordova C, Barbaro M, Troxel A, Silverman J, Snuderl M, Zagzag D, Golfinos J, Kondziolka D, Sulman E. CTNI-57. RADIONUCLIDE THERAPY WITH 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA - INTERIM ANALYSIS RESULTS OF A SINGLE-ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY. Neuro-Oncology 2022, 24: vii85-vii85. DOI: 10.1093/neuonc/noac209.322.Peer-Reviewed Original ResearchSomatostatin receptor 2Progression-free survivalPhase II studyPFS-6Interim analysis resultsII studyIntracranial meningiomasClinical trialsMulticenter phase II studySomatostatin receptor 2 expressionInterim analysisPET-MRITreatment-limiting toxicityAggressive clinical courseCourse of radiationPET-MR imagingMethylation subclassesRadiotherapeutic optionsStable diseaseProgressive meningiomasOverall survivalNeuroendocrine tumorsSSTR2 expressionTumor measurementsTumor resectionSURG-23. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR NEWLY DIAGNOSED AND RECURRENT IDH WILD-TYPE GLIOBLASTOMA
de Groot J, Kim A, Prabhu S, Rao G, Laxton A, Fecci P, O'Brien B, Sloan A, Chiang V, Tatter S, Mohammadi A, Placantonakis D, Strowd R, Chen C, Hadjipanayis C, Khasraw M, Sun D, Piccioni D, Sinicrope K, Campian J, Kurz S, Williams B, Smith K, Tovar-Spinoza Z, Leuthardt E. SURG-23. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR NEWLY DIAGNOSED AND RECURRENT IDH WILD-TYPE GLIOBLASTOMA. Neuro-Oncology 2022, 24: vii256-vii257. PMCID: PMC9660753, DOI: 10.1093/neuonc/noac209.989.Peer-Reviewed Original ResearchLaser interstitial thermal therapyIDH wild-type glioblastomaConventional surgical resectionWild-type glioblastomaInterstitial thermal therapySurgical resectionProspective multicenter registryMaximal safe resectionTime of diagnosisGross total resectionPrimary brain tumorsCytoreductive approachMedian OSAdjuvant temozolomideHospital stayMulticenter registryAdverse eventsOverall survivalRecurrent patientsClinical outcomesRecurrent GBMTraditional resectionMedian lengthSurgical approachTreatment optionsAssociation of hyperglycemia and molecular subclass on survival in IDH-wildtype glioblastoma
Liu E, Vasudevaraja V, Sviderskiy V, Feng Y, Tran I, Serrano J, Cordova C, Kurz S, Golfinos J, Sulman E, Orringer D, Placantonakis D, Possemato R, Snuderl M. Association of hyperglycemia and molecular subclass on survival in IDH-wildtype glioblastoma. Neuro-Oncology Advances 2022, 4: vdac163. PMID: 36382106, PMCID: PMC9653172, DOI: 10.1093/noajnl/vdac163.Peer-Reviewed Original ResearchIDH-wt GBMAssociated with poor OSMethylation subclassesOverall survivalPoor OSIDH-wtMolecular subclassesRTK IAssociated with worse survivalAssociated with OSIDH-wildtype glioblastomaPotential survival benefitAssociation of hyperglycemiaAverage glucose valuesAverage glucoseStupp protocolDexamethasone doseMGMT statusSurvival benefitWorse survivalMesenchymal tumorsPerformance statusLow glucose levelsMGMT methylationMolecular subtypesEfficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma
de Groot JF, Kim AH, Prabhu S, Rao G, Laxton AW, Fecci PE, O’Brien B, Sloan A, Chiang V, Tatter SB, Mohammadi AM, Placantonakis DG, Strowd RE, Chen C, Hadjipanayis C, Khasraw M, Sun D, Piccioni D, Sinicrope KD, Campian JL, Kurz SC, Williams B, Smith K, Tovar-Spinoza Z, Leuthardt EC. Efficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma. Neuro-Oncology Advances 2022, 4: vdac040. PMID: 35611270, PMCID: PMC9122789, DOI: 10.1093/noajnl/vdac040.Peer-Reviewed Original ResearchMedian overall survivalLaser interstitial thermal therapyOverall survivalRecurrent patientsWild-type glioblastomaRecurrent glioblastomaGlioblastoma patientsProspective multicenter registry dataMulticenter registry dataRecurrent glioblastoma patientsChemo/radiationPrimary brain tumorsInterstitial thermal therapyIDH wild-type glioblastomaAdjuvant chemotherapyAdverse eventsImproved survivalClinical outcomesPromoter methylation statusMultivariable differenceSurgical approachTreatment optionsRegistry dataUS CentersTumor volume
2021
NCOG-11. ASSOCIATION OF HYPERGLYCEMIA AND TUMOR SUBCLASS ON SURVIVAL IN IDH-WILDTYPE GLIOBLASTOMA
Liu E, Vasudevaraja V, Sviderskiy V, Feng Y, Tran I, Serrano J, Cordova C, Kurz S, Golfinos J, Sulman E, Placantonakis D, Possemato R, Snuderl M. NCOG-11. ASSOCIATION OF HYPERGLYCEMIA AND TUMOR SUBCLASS ON SURVIVAL IN IDH-WILDTYPE GLIOBLASTOMA. Neuro-Oncology 2021, 23: vi154-vi154. PMCID: PMC8598635, DOI: 10.1093/neuonc/noab196.602.Peer-Reviewed Original ResearchIDH-wt glioblastomaAssociated with poor OSMethylation subclassesDexamethasone doseOverall survivalPoor OSIDH-wtMolecular subclassesAssociated with worse survivalRNA expressionIDH-wildtype glioblastomaPotential survival benefitDNA methylation clustersIsocitrate dehydrogenase (IDH)-wildtypeAssociated with survivalClinical next-generation sequencingPlasma glucose measurementsDNA methylation studiesAverage glucoseNext-generation sequencingStupp protocolMGMT statusMesenchymal tumorsPrognostic significanceSurvival benefit
2020
CTNI-53. SINGLE ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY OF THE RADIONUCLIDE 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA
Kurz S, Zan E, Gurewitz J, Cordova C, Troxel A, Sawaged Z, Sevillano-Torres H, Silverman J, Snuderl M, Zagzag D, Golfinos J, Kondziolka D, Sulman E. CTNI-53. SINGLE ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY OF THE RADIONUCLIDE 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA. Neuro-Oncology 2020, 22: ii54-ii55. PMCID: PMC7651467, DOI: 10.1093/neuonc/noaa215.219.Peer-Reviewed Original ResearchSomatostatin receptor 2Somatostatin receptor 2 expressionProgression-free survivalPhase II studyStandardized uptake valueIntracranial meningiomasPFS-6II studyBackground MeningiomasProgressive diseaseTreatment responseMulticenter phase II studyPET-MRIFunctional treatment responseCourse of radiationPrimary intracranial neoplasmsPET-MR imagingMethylation subclassesRadiotherapeutic optionsStable diseaseCTCAE gradeProgressive meningiomasOverall survivalNeuroendocrine tumorsSSTR2 expressionCTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM)
Lukas R, Chiocca E, Bush N, Landolfi J, Cavaliere R, Yu J, Kurz S, Demars N, Buck J, Hadar N, Miao J, Loewy J, Wang Y, Gelb A, Cooper L. CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM). Neuro-Oncology 2020, 22: ii39-ii39. PMCID: PMC7650356, DOI: 10.1093/neuonc/noaa215.162.Peer-Reviewed Original ResearchPD-1 inhibitorsImmune-mediated anti-tumor effectsAnti-tumor effectsRecurrent glioblastomaIL-12PD-1Overall survivalFollow-upIncreased PD-1 expressionIL-12 therapyPD-1 expressionPhase 2 trialPhase 1 trialPost-treatment biopsiesGene therapy candidateSurvival dataEndogenous cytokine productionIFN-g levelsTumor cell heterogeneityFunctional IL-12Blood-brain barrierCombination immunotherapyIT injectionSafety profileIFN-gCTNI-37. EFFICACY OF ONC201 IN PATIENTS WITH ONC201 FOR RECURRENT H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA
Arrillaga-Romany I, Kurz S, Tarapore R, Sumrall A, Butowski N, Harrison R, de Groot J, Chi A, Shonka N, Umemura Y, Odia Y, Mehta M, Nghiemphu P, Cloughesy T, Taylor L, Graber J, Kilburn L, Dixit K, Lu G, Allen J, Batchelor T, Lassman A, Wen P. CTNI-37. EFFICACY OF ONC201 IN PATIENTS WITH ONC201 FOR RECURRENT H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA. Neuro-Oncology 2020, 22: ii50-ii51. PMCID: PMC7651099, DOI: 10.1093/neuonc/noaa215.204.Peer-Reviewed Original ResearchH3 K27M-mutant diffuse midline gliomaDiffuse midline gliomaRANO criteriaMidline gliomaFrequent drug-related adverse eventsDrug-related adverse eventsCentral radiology reviewContrast-enhancing diseaseObjective response rateProgression-free survivalCerebrospinal fluid disseminationGrade nauseaRadiographic regressionPrior radiationOverall survivalDismal prognosisDRD2 antagonistsMedian agePrimary lesionRadiological reviewMedian timeAdverse eventsT1 contrast enhancementClpP agonistsClinical studiesLTBK-01. INO-5401 AND INO-9012 DELIVERED INTRAMUSCULARLY (IM) WITH ELECTROPORATION (EP) IN COMBINATION WITH CEMIPLIMAB (REGN2810) IN NEWLY DIAGNOSED GLIOBLASTOMA
Reardon D, Brem S, Desai A, Bagley S, Kurz S, De La Fuente M, Nagpal S, Welch M, Hormigo A, Forsyth P, Mandell J, Khagi S, Aiken R, Walbert T, Lieberman F, Portnow J, Batiste J, Carroll N, Sylvester A, Campbell P, Lowy I, Dolgoter A, Boyer J, Kraynyak K, Morrow M, McMullan T, Weiner D, Skolnik J. LTBK-01. INO-5401 AND INO-9012 DELIVERED INTRAMUSCULARLY (IM) WITH ELECTROPORATION (EP) IN COMBINATION WITH CEMIPLIMAB (REGN2810) IN NEWLY DIAGNOSED GLIOBLASTOMA. Neuro-Oncology 2020, 22: ii237-ii237. PMCID: PMC7678727, DOI: 10.1093/neuonc/noaa215.988.Peer-Reviewed Original ResearchCohort AMedian OSAntigen-specific T cell responsesImmune responseRobust systemic immune responsesInterferon-gamma ELISPOTDiagnosed GBM patientsT cell responsesEncoding tumor antigensAdverse event profileNewly diagnosed glioblastomaPeripheral immune responseSystemic immune responsesCheckpoint inhibitionPD-1Diagnosed GBMDiagnosed glioblastomaOverall survivalCohort B.Tumor antigensCD8+T cellsMedian agePrimary endpointCohort BEvent profileSurvival of subjects with recurrent glioblastoma receiving intratumoral administration of controlled IL-12 with limited exposure to dexamethasone.
Lukas R, Kurz S, Yu J, Landolfi J, Rao G, Amidei C, Buck J, Hadar N, Estupinan T, Miao J, Loewy J, Wang Y, Demars N, Gelb A, Cooper L. Survival of subjects with recurrent glioblastoma receiving intratumoral administration of controlled IL-12 with limited exposure to dexamethasone. Journal Of Clinical Oncology 2020, 38: 2564-2564. DOI: 10.1200/jco.2020.38.15_suppl.2564.Peer-Reviewed Original ResearchMedian overall survivalImpact of DexIL-12Intratumoral administrationIFN-gGrade III or IV gliomaImmune-mediated anti-tumor effectsLow-dose corticosteroidsAnti-tumor responsesSerum IL-12Time of resectionTumor response dataRecombinant IL-12Survival of subjectsAnti-tumor effectsExposure to dexamethasoneImmune system activationOverall survivalRecurrent glioblastomaIV gliomasControl edemaPreclinical modelsSafety profileInterleukin-12Historical controlsP858 An open-label, multi-center trial of INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab in subjects with newly-diagnosed glioblastoma (GBM)
Skolnik J, Reardon D, Brem S, Desai A, Bagley S, Kurz S, de la Fuente M, Nagpal S, Welch M, Sacchetta B, Bartra S, Bredlau A, Lowy I, Kraynyak K, Morrow M, McMullan T, Boyer J. P858 An open-label, multi-center trial of INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab in subjects with newly-diagnosed glioblastoma (GBM). Journal For ImmunoTherapy Of Cancer 2020, 8: a8. DOI: 10.1136/lba2019.12.Peer-Reviewed Original ResearchNewly-diagnosed GBMCheckpoint inhibitorsCheckpoint inhibitionOverall survivalCohort ASafety profileClinical efficacyPD-1 checkpoint inhibitorsImmune-related AECycles of temozolomideT cell responsesNewly-diagnosed glioblastomaWeeks of treatmentPreliminary clinical efficacyMulti-center trialInstitutional ethics boardMaintenance temozolomidePD-1Open-labelCohort B.Median agePhase I/IICohort BCemiplimabAdverse events
2019
ATIM-18. SURVIVAL OF SUBJECTS WITH RECURRENT GLIOBLASTOMA RECEIVING INTRA-TUMORAL ADMINISTRATION OF IL-12 MANAGED WITH LOW-DOSE DEXAMETHASONE
Lukas R, Chiocca E, Kurz S, Yu J, Landolfi J, Rao G, Buck J, Demars N, Smith A, Miao J, Zhou J, Wang Y, Gelb A, Cooper L. ATIM-18. SURVIVAL OF SUBJECTS WITH RECURRENT GLIOBLASTOMA RECEIVING INTRA-TUMORAL ADMINISTRATION OF IL-12 MANAGED WITH LOW-DOSE DEXAMETHASONE. Neuro-Oncology 2019, 21: vi5-vi5. PMCID: PMC6847372, DOI: 10.1093/neuonc/noz175.018.Peer-Reviewed Original ResearchLow-dose dexamethasoneIL-12IFN-gIntratumoral injection of AdOngoing phase 1Low-dose corticosteroidsIntra-tumoral administrationProduction of IL-12Drug-related toxicityInjection of AdRecombinant IL-12Induce IL-12Overall survivalIntratumoral injectionDose-relatedDrug-related deathsGene therapyHistorical controlsAnticipated survivalSubject characteristicsSurvival dataSurvivalBiomarker studiesBiomarker analysisBiomarkersEvaluation of controlled IL-12 as monotherapy in subjects with recurrent GBM.
Lukas R, Chiocca E, Kurz S, Yu J, Landolfi J, Rao G, Barrett J, Buck J, Demars N, Smith A, Miao J, Zhou Q, Gelb A, Cooper L. Evaluation of controlled IL-12 as monotherapy in subjects with recurrent GBM. Journal Of Clinical Oncology 2019, 37: 2053-2053. DOI: 10.1200/jco.2019.37.15_suppl.2053.Peer-Reviewed Original ResearchCytokine release syndromeT cell ratioRecurrent glioblastomaIL-12Low-dose DexOverall survivalImmune-mediated anti-tumor effectsIntratumoral injection of AdImmune systemAnti-tumor responsesImproved overall survivalResponse to immunotherapySerum IL-12Replication-incompetent adenovirusCytotoxic T cellsInjection of AdAnti-tumor effectsDay 0Impact of DexFlu-like symptomsIL-12 productionInduce IL-12Biomarkers of OSRecurrent GBMIntratumoral injectionLonger Median Overall Survival in Glioblastoma Patients from Racial and Ethnical Minority Groups (S30.007)
Yu S, Patel A, Crispino S, Utate M, Kurz S. Longer Median Overall Survival in Glioblastoma Patients from Racial and Ethnical Minority Groups (S30.007). Neurology 2019, 92 DOI: 10.1212/wnl.92.15_supplement.s30.007.Peer-Reviewed Original Research