2021
Central Nervous System Metastases
Nieblas-Bedolla E, Zuccato J, Kluger H, Zadeh G, Brastianos PK. Central Nervous System Metastases. Hematology/Oncology Clinics Of North America 2021, 36: 161-188. PMID: 34711458, DOI: 10.1016/j.hoc.2021.08.004.Peer-Reviewed Original ResearchConceptsCentral nervous system metastasesNervous system metastasesBrain metastasesSpinal metastasesExtensive brain metastasesSymptomatic brain metastasesUnstable spinal lesionsWhole brain radiotherapyProportion of patientsSmall brain metastasesCognitive side effectsExternal beam radiotherapyCNS metastasesSurgical resectionSystemic therapyHistological diagnosisSpinal lesionsSurgical biopsySeparation surgeryBeam radiotherapyStereotactic radiosurgerySide effectsMetastasisRadiotherapyResectionAgonistic CD40 Antibodies in Cancer Treatment
Djureinovic D, Wang M, Kluger HM. Agonistic CD40 Antibodies in Cancer Treatment. Cancers 2021, 13: 1302. PMID: 33804039, PMCID: PMC8000216, DOI: 10.3390/cancers13061302.Peer-Reviewed Original ResearchAgonistic CD40 antibodyCD40 antibodyDendritic cellsAntigen presentationClinical developmentEarly phase clinical trialsAgonist CD40 antibodyActivation of CD8Pro-inflammatory effectsAntigen-presenting cellsT cell functionRenal cell carcinomaAnti-tumor effectsPhase clinical trialsAnti-tumor activityT cell activationCancer Genome AtlasSystemic therapyCell carcinomaCostimulatory moleculesCD40 expressionClinical trialsPancreatic adenocarcinomaPreclinical modelsT cells
2020
Cardiac Biventricular Metastasis From Renal Cell Carcinoma
Latifi AN, Ibe U, Arbune A, Kluger H, Baldassarre LA. Cardiac Biventricular Metastasis From Renal Cell Carcinoma. Cureus 2020, 12: e10870. PMID: 33178523, PMCID: PMC7652367, DOI: 10.7759/cureus.10870.Peer-Reviewed Original ResearchRenal cell carcinomaMetastatic renal cell carcinomaCardiac metastasisCell carcinomaRecurrent metastatic renal cell carcinomaCircumferential pericardial effusionSecondary cardiac tumorsAdvanced metastatic diseaseExtent of diseaseShortness of breathSite of involvementCardiac magnetic resonanceCardiac tumorsRespiratory failureMetastatic diseasePericardial effusionSystemic therapyBiventricular hypertrophyMultiple lesionsPrimary tumorPatient's diseaseTissue biopsiesMetastasisVentricular wallDiseaseMelanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trialsSystemic Therapy for Brain Metastases: Melanoma
Weiss S, Kluger H. Systemic Therapy for Brain Metastases: Melanoma. 2020, 235-244. DOI: 10.1007/978-3-030-42958-4_16.Peer-Reviewed Original ResearchMelanoma brain metastasesIntracranial response ratesBrain metastasesClinical trialsResponse rateAnti-PD-1 monotherapyCentral nervous system metastasesExtracranial metastatic sitesNervous system metastasesSystemic therapy approachesMultiple clinical trialsSystemic therapySystemic treatmentAdvanced melanomaImmune checkpointsMetastatic sitesTherapeutic challengePatient survivalMetastatic melanomaExtracranial sitesStereotactic radiosurgeryMetastasisMutant BRAFSignificant causeMEK inhibitionMelanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy
Margolin K, Davies M, Kluger H, Tawbi H. Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy. 2020, 1421-1454. DOI: 10.1007/978-3-030-05070-2_65.Peer-Reviewed Original ResearchMelanoma brain metastasesCentral nervous systemSystemic therapyClinical benefitMainstay of therapyUnique patient populationDuration of responseHigh response rateFuture drug developmentMelanoma metastaticBrain metastasesDevastating complicationDurable responsesImmune checkpointsImmune therapyPatient populationMetastatic melanomaEffective modalityStereotactic radiosurgeryNervous systemResponse rateTherapyMultidisciplinary approachDrug developmentMelanoma
2019
Brain Metastasis From Renal-Cell Carcinoma: An Institutional Study
Suarez-Sarmiento A, Nguyen KA, Syed JS, Nolte A, Ghabili K, Cheng M, Liu S, Chiang V, Kluger H, Hurwitz M, Shuch B. Brain Metastasis From Renal-Cell Carcinoma: An Institutional Study. Clinical Genitourinary Cancer 2019, 17: e1163-e1170. PMID: 31519468, DOI: 10.1016/j.clgc.2019.08.006.Peer-Reviewed Original ResearchConceptsRCC brain metastasesRecurrence-free survivalRenal cell carcinomaBrain metastasesOverall survivalClinical trialsAdvanced renal cell carcinomaCentral nervous system treatmentClear cell renal cell carcinomaMedian overall survivalSingle institution experienceGood local controlKaplan-Meier methodAggressive therapyCNS recurrenceTreatment eraCumulative incidenceExtracranial metastasesMetastatic diseaseSystemic therapyInitial presentationLocal therapyClinical symptomsRCC patientsCell carcinomaMelanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy
Margolin K, Davies M, Kluger H, Tawbi H. Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy. 2019, 1-34. DOI: 10.1007/978-3-319-46029-1_65-1.Peer-Reviewed Original ResearchMelanoma brain metastasesCentral nervous systemSystemic therapyClinical benefitMainstay of therapyUnique patient populationDuration of responseHigh response rateFuture drug developmentMelanoma metastaticBrain metastasesDevastating complicationDurable responsesImmune checkpointsImmune therapyPatient populationMetastatic melanomaEffective modalityStereotactic radiosurgeryNervous systemResponse rateTherapyMultidisciplinary approachDrug developmentMelanoma
2017
Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy.
Sarnaik A, Kluger H, Chesney J, Sethuraman J, Veerapathran A, Simpson-Abelson M, Lotze M, Larsen B, Fischkoff S, Suzuki S, Wang L, Mirgoli M, Fardis M, Curti B. Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 3045-3045. DOI: 10.1200/jco.2017.35.15_suppl.3045.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesAdvanced metastatic melanomaMetastatic melanomaTIL productsPrior therapySafety profileIL-2Advanced metastatic melanoma patientsNon-hematologic grade 3Cell therapyPrior systemic therapyAcceptable safety profilePhase 2 studyMetastatic melanoma patientsAdoptive cell therapyEx vivo expansionEnlisted patientsRECIST 1.1Study patientsCheckpoint therapyMedian durationSurgical resectionSystemic therapyAutologous lymphocytesMedian age
2016
The Treatment of Melanoma Brain Metastases
Kibbi N, Kluger H. The Treatment of Melanoma Brain Metastases. Current Oncology Reports 2016, 18: 73. PMID: 27822695, DOI: 10.1007/s11912-016-0555-4.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesSystemic therapyClinical trialsAsymptomatic brain metastasesPrognosis of patientsUntreated brain metastasesPopulation of patientsOngoing clinical trialsCentral nervous systemMBM patientsCerebral edemaTreatment landscapeImproved survivalIntracranial metastasesMetastatic melanomaStereotactic radiosurgeryNew therapiesLocal modalitiesNervous systemPatientsDrug AdministrationRegistration trialsMetastasisEarly interventionPossible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases
Alomari AK, Cohen J, Vortmeyer AO, Chiang A, Gettinger S, Goldberg S, Kluger HM, Chiang VL. Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases. Cancer Immunology Research 2016, 4: 481-487. PMID: 26994250, DOI: 10.1158/2326-6066.cir-15-0238.Peer-Reviewed Original ResearchConceptsStereotactic radiosurgeryBrain metastasesInitiation of immunotherapyPD-1 mAbImmune-modulating therapyModalities of treatmentRadiologic progressionSurgical resectionSystemic therapyDeath-1Radiologic findingsMetastatic malignancyReactive astrocytosisPathologic examinationTreatment regimensHistopathologic examinationWall infiltrationT lymphocytesPatientsTumor progressionMonoclonal antibodiesBiologic interactionsRadiation-induced changesImmunotherapyMalignancyPD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. New England Journal Of Medicine 2016, 374: 2542-2552. PMID: 27093365, PMCID: PMC4927341, DOI: 10.1056/nejmoa1603702.Peer-Reviewed Original ResearchConceptsAdvanced Merkel cell carcinomaMerkel cell carcinomaObjective response rateVirus-positive tumorsVirus-negative tumorsResponse rateDrug-related grade 3MCPyV-specific T cellsDose of pembrolizumabImmune inhibitory pathwaysPrevious systemic therapyTumor viral statusPD-1 blockadePrimary end pointFirst-line therapyProgression-free survivalResponse Evaluation CriteriaAggressive skin cancerMCPyV-positive tumorsMerkel cell polyomavirusAdverse eventsPartial responseSystemic therapyComplete responsePD-1
2015
Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?
Colaco RJ, Martin P, Kluger HM, Yu JB, Chiang VL. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? Journal Of Neurosurgery 2015, 125: 17-23. PMID: 26544782, DOI: 10.3171/2015.6.jns142763.Peer-Reviewed Original ResearchConceptsTreatment-related imaging changesCytotoxic chemotherapyRadiation necrosisBrain metastasesSystemic therapyStereotactic Gamma Knife radiosurgeryMedian overall survivalGamma knife radiosurgeryHigh-dose radiationChemotherapy eraGK surgeryImmunotherapy increasesMedian followConclusions PatientsOverall survivalImaging changesGK treatmentKnife radiosurgeryInflammatory reactionStereotactic radiosurgeryLower riskRadiosurgical treatmentPatientsImmunotherapyTherapy
2014
Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).
Sznol M, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Atkins M, Kirkwood J, Burke M, Ralabate A, Rivera A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Krishnan S, Gupta A, Wolchok J. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). Journal Of Clinical Oncology 2014, 32: lba9003-lba9003. DOI: 10.1200/jco.2014.32.18_suppl.lba9003.Peer-Reviewed Original ResearchClinical activityTreatment-related adverse eventsMT statusManageable safety profilePrior systemic therapyPhase I trialMajority of ptsBRAF mutation statusBRAF MTIPI therapyStage M1cPrior therapyMedian durationObjective responseSystemic therapyAdvanced melanomaAdverse eventsConcurrent therapyI trialOS ratesSafety profileTumor reductionTumor responseGrade 3Wk 24
2013
Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM).
Hamid O, Sosman J, Lawrence D, Sullivan R, Ibrahim N, Kluger H, Boasberg P, Flaherty K, Hwu P, Ballinger M, Mokatrin A, Kowanetz M, Chen D, Hodi F. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). Journal Of Clinical Oncology 2013, 31: 9010-9010. DOI: 10.1200/jco.2013.31.15_suppl.9010.Peer-Reviewed Original ResearchObjective response rateMM ptsPD-L1Tumor shrinkageAntitumor activityImmunotherapy-responsive diseasePD-L1 overexpressionTreatment-related deathsPD-L1 statusPD-L1 antibodiesHuman monoclonal antibodyInitial antitumor activityPt ageRECIST responseRECIST v1.1Median durationPrior surgeryPS 0Radiographic progressionSystemic therapyElevated ASTPD-1Dose escalationHistologic subtypeInitial treatmentAdvances in therapy for melanoma brain metastases
Flanigan JC, Jilaveanu LB, Chiang VL, Kluger HM. Advances in therapy for melanoma brain metastases. Clinics In Dermatology 2013, 31: 264-281. PMID: 23608446, DOI: 10.1016/j.clindermatol.2012.08.008.Peer-Reviewed Original Research
2012
Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival.
Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. Journal Of Neurosurgery 2012, 117: 227-33. PMID: 22702482, PMCID: PMC6098938, DOI: 10.3171/2012.5.jns111929.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic AgentsBrain NeoplasmsCombined Modality TherapyCompassionate Use TrialsDisease-Free SurvivalFemaleHumansIpilimumabMaleMelanomaMiddle AgedNeoplasm StagingPrognosisProportional Hazards ModelsRadiosurgeryRetreatmentRetrospective StudiesConceptsMelanoma brain metastasesBrain metastasesPerformance statusMedian survivalDiagnosis-Specific Graded Prognostic Assessment (DS-GPA) scoreInstitutional review board-approved chart reviewSurvival rateGraded Prognostic Assessment scoreBrain metastasis diagnosisPrognostic assessment scoreSurvival of patientsNumber of metastasesDS-GPA scoreRadiation therapy usePrimary disease locationBrain oligometastasesIpilimumab groupIpilimumab useSalvage WBRTChart reviewOverall survivalPatient ageSystemic therapyTherapy useClinical variables