2024
Vascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumor
2022
Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities
Karz A, Dimitrova M, Kleffman K, Alvarez‐Breckenridge C, Atkins MB, Boire A, Bosenberg M, Brastianos P, Cahill DP, Chen Q, Ferguson S, Forsyth P, Oliva I, Goldberg SB, Holmen SL, Knisely JPS, Merlino G, Nguyen DX, Pacold ME, Perez‐Guijarro E, Smalley KSM, Tawbi HA, Wen PY, Davies MA, Kluger HM, Mehnert JM, Hernando E. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell & Melanoma Research 2022, 35: 554-572. PMID: 35912544, PMCID: PMC10171356, DOI: 10.1111/pcmr.13059.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesMBM patientsBrain metastasesCheckpoint inhibitor trialsCommon brain malignancyMelanoma Research FoundationDedicated clinical trialsRole of astrocytesNovel treatment approachesImmunotherapy trialsInhibitor trialsBrain malignanciesClinical trialsPatient outcomesBrain microenvironmentTreatment approachesPatient advocatesPatientsTrialsTherapeutic purposesMetabolic adaptationMetastasisCurrent standardTherapyRecent reportsEmerging Studies of Melanoma Brain Metastasis
Caulfield JI, Kluger HM. Emerging Studies of Melanoma Brain Metastasis. Current Oncology Reports 2022, 24: 585-594. PMID: 35212922, DOI: 10.1007/s11912-022-01237-9.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesClinical studiesTreatment approachesRecent FindingsClinical trialsImmune checkpoint inhibitorsAdditional treatment approachesRecent preclinical studiesNew treatment approachesCentral nervous systemBrain disseminationCheckpoint inhibitorsSignificant morbidityPerilesional edemaRadiation necrosisPatient populationClinical challengePreclinical studiesNervous systemSolid tumorsEmerging studiesMetastasisTumor microenvironmentDisease controlTumor homing
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 effectsMetastasisRadiotherapyResectionTumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling
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 wallDisease19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA
Oria V, Zhang H, Zhu H, Deng G, Zito C, Rane C, Zhang S, Weiss S, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg M, Kluger H, Jilaveanu L. 19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA. Neuro-Oncology Advances 2020, 2: ii3-ii3. PMCID: PMC7401364, DOI: 10.1093/noajnl/vdaa073.009.Peer-Reviewed Original ResearchMelanoma brain metastasesBrain metastasesTumor growthPI3K/Akt/mTORCell cycle transitionAkt/mTORGrowth of tumorsS cell cycle transitionPhosphorylation of AktMelanoma patientsPoor prognosisNovel drug targetsPatient populationRegulation of PDCD4Metastatic melanomaUnique cohortXenograft modelClinical relevanceNude miceMetastasisCycle transitionMelanomaBrain developmentKey mediatorMelanoma cellsSystemic 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 inhibitionLeptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions
Glitza IC, Smalley KSM, Brastianos PK, Davies MA, McCutcheon I, Liu JKC, Ahmed KA, Arrington JA, Evernden BR, Smalley I, Eroglu Z, Khushalani N, Margolin K, Kluger H, Atkins MB, Tawbi H, Boire A, Forsyth P. Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions. Pigment Cell & Melanoma Research 2020, 33: 527-541. PMID: 31916400, PMCID: PMC10126834, DOI: 10.1111/pcmr.12861.Peer-Reviewed Original ResearchConceptsLeptomeningeal diseaseMelanoma patientsCentral nervous system metastasesMelanoma Research FoundationParenchymal brain metastasesNervous system metastasesMoffitt Cancer CenterMultiple academic centersBrain metastasesCancer CenterTherapeutic managementAcademic centersClinical researchDeadly diseaseConsensus summaryDiseasePatientsMetastasisSecond summit[11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis
Tran TT, Gallezot JD, Jilaveanu LB, Zito C, Turcu G, Lim K, Nabulsi N, Huang H, Huttner A, Kluger HM, Chiang VL, Carson R. [11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis. Molecular Imaging 2020, 19: 1536012120968669. PMID: 33147119, PMCID: PMC7649862, DOI: 10.1177/1536012120968669.Peer-Reviewed Original ResearchConceptsRadiation necrosisTumor regrowthStereotactic radiosurgeryBrain metastasesPET tracersHigh amino acid uptakeMetastatic tumor recurrenceLung cancer cellsSpecific PET tracersPET imaging tracerTumor recurrenceAmino acid uptakeImaging tracerReliable markerDiagnostic imagingLack of specificityAcid uptakeCancer cellsSpecific markersMethionine levelsTranslocator proteinSequential imagingInflammationMetastasisDual tracer
2019
Complications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatientsFrequent Use of Local Therapy Underscores Need for Multidisciplinary Care in the Management of Patients With Melanoma Brain Metastases Treated With PD-1 Inhibitors
Qian JM, Yu JB, Mahajan A, Goldberg SB, Kluger HM, Chiang VLS. Frequent Use of Local Therapy Underscores Need for Multidisciplinary Care in the Management of Patients With Melanoma Brain Metastases Treated With PD-1 Inhibitors. International Journal Of Radiation Oncology • Biology • Physics 2019, 105: 1113-1118. PMID: 31479702, DOI: 10.1016/j.ijrobp.2019.08.053.Peer-Reviewed Original ResearchConceptsBrain metastasesLocal therapyNeurologic safetyMelanoma patientsProspective phase 2 trialProgressive brain metastasesSerial brain imagingMelanoma brain metastasesPD-1 inhibitorsPhase 2 trialRapid disease progressionManagement of patientsNeurologic symptomsMultidisciplinary careTrial enrollmentCystic changesClinical trialsDisease progressionPatientsLesion sizeMetastasisMultidisciplinary teamTumor growthTherapyClinical decisionTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.Peer-Reviewed Original ResearchConceptsBrain metastasesBrain tumor microenvironmentLineage programTumor microenvironmentTumor plasticityStromal gene expressionTranscriptomic hallmarksGene expressionTranscriptional hallmarksMultiple tumor typesMolecular landscapeStromal interactionsMajor siteIntact tissueNeuroinflammatory responseSyngeneic modelPatient biopsiesTumor typesMetastasisMalignant cellsDifferent subtypesTumor cellsHallmarkTranscriptomeCellsMelanoma central nervous system metastases: An update to approaches, challenges, and opportunities
Eroglu Z, Holmen SL, Chen Q, Khushalani NI, Amaravadi R, Thomas R, Ahmed KA, Tawbi H, Chandra S, Markowitz J, Smalley I, Liu JKC, Chen YA, Najjar YG, Karreth FA, Abate‐Daga D, Glitza IC, Sosman JA, Sondak VK, Bosenberg M, Herlyn M, Atkins MB, Kluger H, Margolin K, Forsyth PA, Davies MA, Smalley KSM. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell & Melanoma Research 2019, 32: 458-469. PMID: 30712316, PMCID: PMC7771318, DOI: 10.1111/pcmr.12771.Peer-Reviewed Original Research
2018
Perilesional edema and blood vessel characteristics in brain metastases and implications for treatment with immune therapy.
Tran T, Jilaveanu L, Mahajan A, Goldberg S, Nguyen D, Chiang V, Kluger H. Perilesional edema and blood vessel characteristics in brain metastases and implications for treatment with immune therapy. Journal Of Clinical Oncology 2018, 36: 9572-9572. DOI: 10.1200/jco.2018.36.15_suppl.9572.Peer-Reviewed Original Research
2016
Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells
Boddupalli CS, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM. Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight 2016, 1: e88955. PMID: 28018970, PMCID: PMC5161225, DOI: 10.1172/jci.insight.88955.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesMemory T cellsTissue-resident memory T cellsT cell receptorImmune checkpointsT cellsIndividual metastasesSubset of TILsExpression of ICsCell receptorTumor cellsLess IL-2Blood T cellsExpression of VEGFTIL infiltrationDurable responsesAdvanced melanomaImmune therapyNeoantigen loadIL-2Immune cellsNonlymphoid tissuesSame patientMyeloid cellsMetastasisThe 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 interventionMelanoma central nervous system metastases: current approaches, challenges, and opportunities
Cohen JV, Tawbi H, Margolin KA, Amravadi R, Bosenberg M, Brastianos PK, Chiang VL, de Groot J, Glitza IC, Herlyn M, Holmen SL, Jilaveanu LB, Lassman A, Moschos S, Postow MA, Thomas R, Tsiouris JA, Wen P, White RM, Turnham T, Davies MA, Kluger HM. Melanoma central nervous system metastases: current approaches, challenges, and opportunities. Pigment Cell & Melanoma Research 2016, 29: 627-642. PMID: 27615400, PMCID: PMC5398760, DOI: 10.1111/pcmr.12538.Peer-Reviewed Original ResearchMelanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment
Cohen JV, Alomari AK, Vortmeyer AO, Jilaveanu LB, Goldberg SB, Mahajan A, Chiang VL, Kluger HM. Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. Cancer Immunology Research 2016, 4: 179-182. PMID: 26701266, PMCID: PMC4881844, DOI: 10.1158/2326-6066.cir-15-0160.Peer-Reviewed Original ResearchConceptsCentral nervous systemBrain metastasesActive brain lesionsNew immunomodulating agentsImmune checkpoint inhibitorsRole of immunotherapyPembrolizumab treatmentCheckpoint inhibitorsCNS lesionsReactive astrocytosisImmune suppressionPerilesional edemaInflammatory cellsMicroglial cellsImmunomodulating agentMental statusBrain lesionsHistologic evaluationMost trialsNervous systemCentral enhancementTumor cellsPatientsMetastasisLesions
2015
Melanoma: Clinical Presentations
Kibbi N, Kluger H, Choi JN. Melanoma: Clinical Presentations. Cancer Treatment And Research 2015, 167: 107-129. PMID: 26601860, DOI: 10.1007/978-3-319-22539-5_4.Peer-Reviewed Original ResearchConceptsNon-cutaneous lesionsUpper gastrointestinal mucosaMalignant skin lesionsGenital mucosaUveal tractClinical presentationDistant metastasisCutaneous lesionsPattern of spreadTypical presentationGastrointestinal mucosaSkin lesionsOral cavityMucosal surfacesMalignant cellsMelanomaRed lesionsLesionsRegional spreadBasal layerMucosaMelanocytesPresentationLeptomeningesMetastasis