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
2019
Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death
Kulkarni PM, Robinson EJ, Pradhan J, Gartrell-Corrado RD, Rohr BR, Trager MH, Geskin LJ, Kluger HM, Wong PF, Acs B, Rizk EM, Yang C, Mondal M, Moore MR, Osman I, Phelps R, Horst BA, Chen ZS, Ferringer T, Rimm DL, Wang J, Saenger YM. Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death. Clinical Cancer Research 2019, 26: 1126-1134. PMID: 31636101, PMCID: PMC8142811, DOI: 10.1158/1078-0432.ccr-19-1495.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsArea Under CurveBiopsyDeep LearningDisease ProgressionFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedMaleMelanomaMiddle AgedNeoplasm Recurrence, LocalNeural Networks, ComputerRetrospective StudiesRisk FactorsStaining and LabelingSurvival RateYoung AdultConceptsDeep neural network architectureNeural network architectureDeep learningNetwork architectureComputational modelImage sequencesDigital imagesVote aggregationDisease-specific survivalDSS predictionPractical advancesComputational methodsIHC-based methodsImagesGeisinger Health SystemNovel methodGHS patientsArchitectureLearningKaplan-Meier analysisPrimary melanoma tumorsEarly-stage melanomaClinical trial designModelAdjuvant immunotherapyTreatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma
Regan MM, Werner L, Rao S, Gupte-Singh K, Hodi FS, Kirkwood JM, Kluger HM, Larkin J, Postow MA, Ritchings C, Sznol M, Tarhini AA, Wolchok JD, Atkins MB, McDermott DF. Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma. Journal Of Clinical Oncology 2019, 37: 3350-3358. PMID: 31498030, PMCID: PMC6901280, DOI: 10.1200/jco.19.00345.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsTreatment-free survivalHigher treatment-related adverse eventsKaplan-Meier curvesTherapy initiationAdvanced melanomaICI therapyEnd pointGrade 3Outcome measuresLonger treatment-free survivalImmuno-oncology agentsSystemic therapy initiationThird end pointTreatment-free timeImmune checkpoint inhibitionSurvival end pointsEvent end pointsNovel outcome measuresCheckMate 067ICI cessationAdverse eventsTherapy cessationCheckpoint inhibitionPooled analysis
2016
Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger H, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-3894. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.can-15-1524.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBlotting, WesternCase-Control StudiesCell CycleCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesMacrophagesMaleMelanomaMiceMice, Inbred C57BLMice, NudeMonoamine OxidaseNeoplasm StagingP38 Mitogen-Activated Protein KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionSTAT3 Transcription FactorSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsTumor-associated macrophagesDisease-specific survivalManagement of melanomaPotential therapeutic implicationsCell cycle inhibitor p21Melanoma cell growthPI3K/AktMelanoma cell survivalCell growth arrestPathogenic rolePrimary melanomaToxic injuryMurine xenograftsTherapeutic implicationsTumor growthClinical specimensRenalaseBax activationTumor microenvironmentTumor cellsInhibitor p21Growth arrestSurvival factorElevated expressionMAPK pathwayTiming and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery
Qian JM, Yu JB, Kluger HM, Chiang VL. Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 2016, 122: 3051-3058. PMID: 27285122, PMCID: PMC5030143, DOI: 10.1002/cncr.30138.Peer-Reviewed Original ResearchConceptsMedian percent reductionImmune checkpoint therapyLesional responseStereotactic radiosurgeryCheckpoint therapyLesion volumeAnti-cytotoxic T-lymphocyte-associated protein 4Anti-programmed cell death protein 1T-lymphocyte-associated protein 4Anti-PD-1 therapyGreater median percent reductionsCell death protein 1Administration of immunotherapyWeeks of immunotherapyMelanoma brain metastasesDeath protein 1Type of immunotherapyWilcoxon rank sum testRank sum testNonconcurrent therapyBrain metastasesMelanoma patientsTreatment of cancerSingle institutionPercent reductionPembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohort
2014
Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib
Wilson MA, Zhao F, Letrero R, D'Andrea K, Rimm DL, Kirkwood JM, Kluger HM, Lee SJ, Schuchter LM, Flaherty KT, Nathanson KL. Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib. Clinical Cancer Research 2014, 20: 3328-3337. PMID: 24714776, PMCID: PMC4058354, DOI: 10.1158/1078-0432.ccr-14-0093.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinDouble-Blind MethodFemaleFollow-Up StudiesGenotypeGTP PhosphohydrolasesHumansMaleMelanomaMembrane ProteinsMiddle AgedMutationNeoplasm StagingNiacinamidePaclitaxelPhenylurea CompoundsPrognosisProto-Oncogene Proteins B-rafSkin NeoplasmsSorafenibSurvival RateConceptsProgression-free survivalNRAS-mutant melanomaPlatelet-derived growth factor receptorPerformance statusClinical outcomesNRAS mutationsCox proportional hazards modelVEGF receptorsSomatic mutationsWorse performance statusGood performance statusImproved clinical responseKaplan-Meier methodClinical trial populationsPretreatment tumor samplesSite of diseaseProportional hazards modelEffect of sorafenibBRAF-mutant melanomaFisher's exact testGrowth factor receptorClinical responseOverall survivalClinicopathologic featuresMelanoma patientsSurvival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2014, 32: 1020-1030. PMID: 24590637, PMCID: PMC4811023, DOI: 10.1200/jco.2013.53.0105.Peer-Reviewed Original ResearchConceptsLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1
2009
Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms
Rothberg BE, Berger AJ, Molinaro AM, Subtil A, Krauthammer MO, Camp RL, Bradley WR, Ariyan S, Kluger HM, Rimm DL. Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms. Journal Of Clinical Oncology 2009, 27: 5772-5780. PMID: 19884546, PMCID: PMC2792999, DOI: 10.1200/jco.2009.22.8239.Peer-Reviewed Original ResearchConceptsHigh-risk groupGrowth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer
Nadler Y, González AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Annals Of Oncology 2009, 21: 466-473. PMID: 19717535, PMCID: PMC2826097, DOI: 10.1093/annonc/mdp346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularFemaleFluorescent Antibody TechniqueFollow-Up StudiesGRB7 Adaptor ProteinHumansImage Processing, Computer-AssistedMiddle AgedPrognosisReceptor, ErbB-2Survival RateTissue Array AnalysisTumor Cells, CulturedYoung AdultConceptsHER2/neuBreast cancerPrognostic markerHER2/neu-positive breast cancerGRB7 expressionHigh HER2/neuNeu-positive breast cancerHER2/neu overexpressionPrimary breast cancerBreast cancer patientsIndependent prognostic markerNode-positive subsetValuable prognostic markerProtein 7Cy5-conjugated antibodiesMultivariable analysisWorse prognosisEntire cohortCancer patientsNeu overexpressionTissue microarrayTherapeutic targetCancerNeuPatients
2004
Automated Quantitative Analysis of HDM2 Expression in Malignant Melanoma Shows Association with Early-Stage Disease and Improved Outcome
Berger AJ, Camp RL, DiVito KA, Kluger HM, Halaban R, Rimm DL. Automated Quantitative Analysis of HDM2 Expression in Malignant Melanoma Shows Association with Early-Stage Disease and Improved Outcome. Cancer Research 2004, 64: 8767-8772. PMID: 15574789, DOI: 10.1158/0008-5472.can-04-1384.Peer-Reviewed Original ResearchConceptsMurine double minute 2Double minute 2Protein expressionMalignant melanomaMinute 2Early-stage diseaseTissue microarray cohortPotential tissue biomarkersCutaneous malignant melanomaValuable prognostic toolNormal skin samplesSkin cancer deathsMicroarray cohortAdvanced melanomaMetastatic lesionsCancer deathPrimary melanomaImproved outcomesExpression of HDM2Tissue biomarkersPrognostic toolBetter outcomesMelanoma lesionsAggressive natureMelanomaAutomated 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 advantageMacrophage 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