2022
Association Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US
Ermer T, Canavan ME, Maduka RC, Li AX, Salazar MC, Kaminski MF, Pichert MD, Zhan PL, Mase V, Kluger H, Boffa DJ. Association Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US. JAMA Network Open 2022, 5: e2219535. PMID: 35771575, PMCID: PMC9247736, DOI: 10.1001/jamanetworkopen.2022.19535.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerRenal cell carcinomaUse of immunotherapyFDA approvalImmunotherapy useCohort studyClinical trialsNovel therapiesStage IV non-small cell lung cancerMultivariable logistic regression modelingFirst checkpoint inhibitorCheckpoint inhibitor therapyNational Cancer DatabasePatients 20 yearsCell lung cancerSocioeconomic strataTreatment of patientsDrug Administration approvalLife-saving treatmentReceipt of immunotherapyLogistic regression modelingSocioeconomic characteristicsImmunotherapy administrationCheckpoint inhibitorsPatient characteristics
2020
Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck
Jacobs D, Olino K, Park HS, Clune J, Cheraghlou S, Girardi M, Burtness B, Kluger H, Judson BL. Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck. Otolaryngology 2020, 164: 1214-1221. PMID: 33079010, DOI: 10.1177/0194599820967001.Peer-Reviewed Original ResearchConceptsNode-negative Merkel cell carcinomaLymph node evaluationImproved overall survivalPrimary tumor excisionMerkel cell carcinomaCase volumeOverall survivalSurgical managementCell carcinomaTumor excisionTreatment selectionNode evaluationCox proportional hazards regressionGuideline-recommended carePrimary treatment selectionNational Cancer DatabaseNode-negative diseasePercentage of patientsRetrospective cohort analysisInitial surgical managementKaplan-Meier analysisWide local excisionProportional hazards regressionRates of receiptInitial management
2018
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial
Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, Weiss SA, Cohen JV, Yu J, Hegde U, Perrotti E, Anderson G, Ralabate A, Kluger Y, Wei W, Goldberg SB, Jilaveanu LB. Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Journal Of Clinical Oncology 2018, 37: 52-60. PMID: 30407895, PMCID: PMC6354772, DOI: 10.1200/jco.18.00204.Peer-Reviewed Original ResearchConceptsBrain metastasis responseBrain metastasesMetastasis responseAdverse eventsAnti-programmed cell death-1 (PD-1) agentsDeath ligand 1 (PD-L1) expressionModified Response Evaluation CriteriaPhase II clinical trialActive brain metastasesAsymptomatic brain metastasesCD8 cell densityNeurologic adverse eventsPembrolizumab-treated patientsUse of pembrolizumabMelanoma brain metastasesPrimary end pointLigand 1 expressionPhase II trialResponse Evaluation CriteriaT-cell infiltratesUntreated brain metastasesDeath ligand 1Two-year survivalOverall survival timeResult of progressionResults of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma
Hellerstedt BA, Vogelzang NJ, Kluger HM, Yasenchak CA, Aftab DT, Ramies DA, Gordon MS, Lara P. Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma. Clinical Lung Cancer 2018, 20: 74-81.e1. PMID: 30528315, DOI: 10.1016/j.cllc.2018.10.006.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMedian progression-free survivalCell lung carcinomaWeek 12Adverse eventsDiscontinuation trialLung carcinomaTreatment-related grade 5 adverse eventsCommon grade 3/4 adverse eventsBioavailable tyrosine kinase inhibitorGrade 3/4 adverse eventsGrade 5 adverse eventsOverall disease control rateSolid Tumors version 1.0Epidermal growth factor receptor (EGFR) mutationsOpen-label leadPhase II PlaceboRandomized discontinuation trialDisease control ratePalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaGrowth factor receptor 2Vascular endothelial growth factor receptor 2Endothelial growth factor receptor 2
2017
Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients
Sanmamed MF, Perez-Gracia JL, Schalper KA, Fusco JP, Gonzalez A, Rodriguez-Ruiz ME, Oñate C, Perez G, Alfaro C, Martín-Algarra S, Andueza MP, Gurpide A, Morgado M, Wang J, Bacchiocchi A, Halaban R, Kluger H, Chen L, Sznol M, Melero I. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients. Annals Of Oncology 2017, 28: 1988-1995. PMID: 28595336, PMCID: PMC5834104, DOI: 10.1093/annonc/mdx190.Peer-Reviewed Original ResearchConceptsSerum IL-8 levelsIL-8 levelsCell lung cancer patientsLung cancer patientsNSCLC patientsCancer patientsMelanoma patientsPD1/PD-L1 therapyAnti-PD-1 treatmentAnti-PD-1 blockadeSerum interleukin-8 levelsPD-L1 therapyImmune checkpoint blockadeInterleukin-8 levelsLonger overall survivalBiomarkers of responseMann-Whitney testCheckpoint blockadeFirst doseOverall survivalStrength of associationClinical benefitReceiver operation characteristic curveMetastatic melanomaSurrogate biomarker
2015
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC, Brahmer JR, Carvajal RD, Hammers HJ, Puzanov I, Hodi FS, Kluger HM, Topalian SL, Pardoll DM, Wigginton JM, Kollia GD, Gupta A, McDonald D, Sankar V, Sosman JA, Atkins MB. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab. Journal Of Clinical Oncology 2015, 33: 2013-2020. PMID: 25800770, PMCID: PMC4517051, DOI: 10.1200/jco.2014.58.1041.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Renal CellCohort StudiesDisease-Free SurvivalDose-Response Relationship, DrugFemaleHumansKidney NeoplasmsMaleMaximum Tolerated DoseMiddle AgedNivolumabPatient SafetyProgrammed Cell Death 1 ReceptorTime FactorsTreatment OutcomeConceptsAdvanced renal cell carcinomaRenal cell carcinomaLong-term safetyOverall survivalDurable responsesTreatment-refractory solid tumorsTreatment-related adverse eventsOngoing randomized clinical trialsImpact of nivolumabMedian overall survivalMedian response durationPortion of patientsDuration of responseRandomized clinical trialsDrug discontinuationIntravenous nivolumabStable diseaseExpansion cohortTreatment discontinuationAdverse eventsObjective responseAdditional patientsAntibody nivolumabCell surface moleculesCell carcinoma
2014
NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma
Giesen E, Jilaveanu LB, Parisi F, Kluger Y, Camp RL, Kluger HM. NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma. Oncotarget 2014, 5: 5209-5217. PMID: 24970819, PMCID: PMC4170640, DOI: 10.18632/oncotarget.2101.Peer-Reviewed Original ResearchConceptsNY-ESO-1 expressionNY-ESO-1Renal cell carcinomaCell carcinomaMetastatic sitesRenal tissueCancer-testis antigen NY-ESO-1Antigen NY-ESO-1Adjacent normal renal tissuesClear cell renal cell carcinomaRCC specimensMetastatic RCC specimensPapillary renal cell carcinomaCell renal cell carcinomaPotential immunotherapeutic targetAdoptive cell therapySubset of RCCTumor-specific antigensClear cell carcinomaNovel immune therapiesPrimary RCC specimensBenign renal tissueNormal renal tissueDifferent tumor sitesImmune therapy
2013
Vascularity of primary and metastatic renal cell carcinoma specimens
Aziz SA, Sznol J, Adeniran A, Colberg JW, Camp RL, Kluger HM. Vascularity of primary and metastatic renal cell carcinoma specimens. Journal Of Translational Medicine 2013, 11: 15. PMID: 23316728, PMCID: PMC3561185, DOI: 10.1186/1479-5876-11-15.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMicrovessel areaMetastatic samplesCell carcinomaMetastatic sitesPrimary tumorMetastatic renal cell carcinomaRenal cell carcinoma tumorsClear cell tumorsClear cell carcinomaPredictive biomarker studiesAnti-angiogenic drugsAnti-angiogenic therapyTypes of tumorsHigh response ratePrimary nephrectomyHistologic subtypeCell tumorsDifferent histologyPapillary histologyCD 34Variable histologyClinical studiesClear cellsTumor vascularity
2011
Melanoma Brain Metastases: Is It Time to Reassess the Bias?
Flanigan JC, Jilaveanu LB, Faries M, Sznol M, Ariyan S, Yu JB, Knisely JP, Chiang VL, Kluger HM. Melanoma Brain Metastases: Is It Time to Reassess the Bias? Current Problems In Cancer 2011, 35: 200-210. PMID: 21911183, PMCID: PMC3173717, DOI: 10.1016/j.currproblcancer.2011.07.003.Peer-Reviewed Original Research
2009
C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Jilaveanu LB, Zito CR, Aziz SA, Conrad PJ, Schmitz JC, Sznol M, Camp RL, Rimm DL, Kluger HM. C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas. Clinical Cancer Research 2009, 15: 5704-5713. PMID: 19737955, PMCID: PMC2763114, DOI: 10.1158/1078-0432.ccr-09-0198.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBenzenesulfonatesCell Line, TumorCell ProliferationCell SurvivalCohort StudiesDisease ProgressionFemaleGene SilencingHumansIndolesMaleMelanomaMiddle AgedNevusNiacinamidePhenolsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafPyridinesRNA, Small InterferingSensitivity and SpecificitySkin NeoplasmsSorafenibYoung AdultConceptsExtracellular signal-regulated kinaseC-RafC-Raf expressionSubset of melanomasPhospho-c-RafSignal-regulated kinaseCell linesProtein kinase inhibitionMitogen-activated protein kinase inhibitionDecreased viabilityDecreased Bcl-2 expressionProtein kinaseCell signalingBcl-2 inhibitionRaf kinaseB-RafMelanoma cell linesPhospho-MEKSpecific siRNAsSitu protein expressionGW5074Major isoformsKinasePhospho-ERKBcl-2 expressionRegulation of non-AU-rich element containing c-fms proto-oncogene expression by HuR in breast cancer
Woo HH, Zhou Y, Yi X, David CL, Zheng W, Gilmore-Hebert M, Kluger HM, Ulukus EC, Baker T, Stoffer JB, Chambers SK. Regulation of non-AU-rich element containing c-fms proto-oncogene expression by HuR in breast cancer. Oncogene 2009, 28: 1176-1186. PMID: 19151756, DOI: 10.1038/onc.2008.469.Peer-Reviewed Original ResearchConceptsBreast cancerBreast cancer tissue arrayNuclear HuR expressionBreast cancer progressionC-fmsC-fms proto-oncogene expressionNodal metastasisPoor prognosisPoor survivalProto-oncogene c-fmsProto-oncogene expressionBreast tumorsGlucocorticoid stimulationTissue arraysCancer progressionHuR expressionRNA expressionDirect targetC-fms mRNACancer biologyC-fms RNACancer
2008
Assessing Expression of Apoptotic Markers Using Large Cohort Tissue Microarrays
Pick E, McCarthy MM, Kluger HM. Assessing Expression of Apoptotic Markers Using Large Cohort Tissue Microarrays. Methods In Molecular Biology 2008, 414: 83-93. PMID: 18175814, DOI: 10.1007/978-1-59745-339-4_8.Peer-Reviewed Original ResearchConceptsLarge cohortApoptotic markersParaffin-embedded specimensHundreds of patientsAnti-apoptotic elementsTissue microarray technologySitu protein expressionApoptotic marker expressionTissue microarrayMarker expressionBenign cellsImmunohistochemistryProtein expressionExtrinsic pathwayExpression levelsCohortMarkersExpressionCellsPatients
2004
Automated Quantitative Analysis of Tissue Microarrays Reveals an Association between High Bcl-2 Expression and Improved Outcome in Melanoma
DiVito KA, Berger AJ, Camp RL, Dolled-Filhart M, Rimm DL, Kluger HM. Automated Quantitative Analysis of Tissue Microarrays Reveals an Association between High Bcl-2 Expression and Improved Outcome in Melanoma. Cancer Research 2004, 64: 8773-8777. PMID: 15574790, DOI: 10.1158/0008-5472.can-04-1387.Peer-Reviewed Original ResearchConceptsBcl-2 expressionHigh Bcl-2 expressionTissue microarrayMetastatic specimensResponse rateSmall cohortProgression-free survivalImproved response ratesLarge patient cohortMelanoma patientsClark levelEntire cohortBreslow depthClinical variablesPatient cohortMetastatic melanomaContinuous index scoreBetter outcomesIndex scoreMelanoma specimensCohortMelanomaBcl-2PatientsOutcomesExpression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas. Cancer Research 2004, 64: 5270-5282. PMID: 15289333, DOI: 10.1158/0008-5472.can-04-0731.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell Transformation, NeoplasticCohort StudiesDown-RegulationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMelanocytesMelanomaMiceNuclear ProteinsOligonucleotide Array Sequence AnalysisPrognosisSignal TransductionSkin NeoplasmsSurvival RateTranscription FactorsTransfectionTwist-Related Protein 1Ubiquitin ThiolesteraseConceptsGlobal differential gene expressionMembrane trafficking eventsNovel pathwayNormal melanocytesHelix protein TwistAdditional transcriptional regulatorsDifferential gene expressionMelanoma cellsTransformation of melanocytesCpG promoter methylationNormal human melanocytesTrafficking eventsTranscriptional regulatorsEmbryonic developmentGrowth suppressorChromosomal regionsExpression profilingGene expressionNotch pathwayOligonucleotide microarraysMelanoma tissue microarrayDifferential expressionGenesHuman melanocytesGrowth advantageHer2/neu is not a commonly expressed therapeutic target in melanoma – a large cohort tissue microarray study
Kluger HM, DiVito K, Berger AJ, Halaban R, Ariyan S, Camp RL, Rimm DL. Her2/neu is not a commonly expressed therapeutic target in melanoma – a large cohort tissue microarray study. Melanoma Research 2004, 14: 207-210. PMID: 15179190, DOI: 10.1097/01.cmr.0000130874.33504.2f.Peer-Reviewed Original ResearchConceptsHER2/neu expressionHER2/neuNeu expressionMelanoma specimensNeu stainingMelanoma patientsLarge cohortPositive HER2/neu expressionChemotherapy-resistant malignancyPrimary cutaneous lesionNumerous new agentsTissue microarray studyMonoclonal antibody trastuzumabAdjuvant therapyCutaneous specimensTrastuzumab therapyMetastatic lesionsBreslow depthClark levelClinicopathological dataCutaneous lesionsPrimary lesionTumor stageMetastatic melanomaBreast cancerMacrophage Colony-Stimulating Factor-1 Receptor Expression Is Associated with Poor Outcome in Breast Cancer by Large Cohort Tissue Microarray Analysis
Kluger HM, Dolled-Filhart M, Rodov S, Kacinski BM, Camp RL, Rimm DL. Macrophage Colony-Stimulating Factor-1 Receptor Expression Is Associated with Poor Outcome in Breast Cancer by Large Cohort Tissue Microarray Analysis. Clinical Cancer Research 2004, 10: 173-177. PMID: 14734466, DOI: 10.1158/1078-0432.ccr-0699-3.Peer-Reviewed Original ResearchConceptsNode-positive patientsNode-negative patientsNode-positive casesCSF-1R expressionBreast cancerNodal statusOverall survivalPoor outcomeIpsilateral breast cancer recurrenceInvasive breast cancerNonmetastatic breast cancerPredictors of survivalNode-negative casesLarger tumor sizeSmall cohort studiesBreast cancer recurrenceCSF-1RTissue microarray analysisMacrophage colony-stimulating factor 1 receptorFactor 1 receptorTransmembrane tyrosine kinase receptorTyrosine kinase receptorsCohort studyColony-stimulating factor 1 receptorNodal involvement
2003
Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival.
Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, Rimm DL. Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Research 2003, 63: 8103-7. PMID: 14678960.Peer-Reviewed Original ResearchConceptsATF2 expressionTranscription factor 2Melanoma specimensUseful prognostic markerEarly-stage melanomaWeak cytoplasmic stainingStrong nuclear stainingFactor 2Mean followCutaneous specimensLocalized diseaseOverall survivalIndependent predictorsPreclinical findingsClark levelClinicopathological dataPatient survivalPoor outcomePrognostic valueWorse outcomesPrognostic markerPoor survivalPreclinical modelsClinical significanceImmunohistochemical staining