2021
Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells
Tran TT, Rane CK, Zito CR, Weiss SA, Jessel S, Lucca L, Lu BY, Oria VO, Adeniran A, Chiang VL, Omay SB, Hafler DA, Kluger HM, Jilaveanu LB. Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers 2021, 13: 1049. PMID: 33801444, PMCID: PMC7958624, DOI: 10.3390/cancers13051049.Peer-Reviewed Original ResearchPDCD4 expressionImproved survivalTumor-Associated Immune CellsTumor microenvironmentNeoplastic progressionBrain metastasis outcomesExtracranial metastatic diseaseMelanoma brain metastasesNatural killer cellsBrain metastasis samplesImmune cell infiltrationImmune cell subsetsMultiple tissue microarraysExpression of PDCD4Brain metastasesMetastatic diseaseClinical outcomesKiller cellsClinicopathological variablesIntracranial metastasesCell subsetsCell infiltrationCell death 4Immune cellsPrimary melanoma
2020
An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status
Ahluwalia M, Ali MA, Joshi RS, Park ES, Taha B, McCutcheon I, Chiang V, Hong A, Sinclair G, Bartek J, Chen CC. An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status. Neuro-Oncology Advances 2020, 3: vdaa152. PMID: 33506199, PMCID: PMC7810198, DOI: 10.1093/noajnl/vdaa152.Peer-Reviewed Original ResearchCumulative intracranial tumor volumeNumber of metastasesBRAF mutation statusMelanoma brain metastasesBrain metastasesStereotactic radiosurgeryMutation statusPrognostic scalesMelanoma patientsSurvival prognosticationIndependent cohortMultivariate Cox proportional hazards modelCox proportional hazards modelIntracranial tumor volumePrognostic assessment scaleMulti-institutional collaborationNet reclassification indexProportional hazards modelBM patientsMainstay therapyPatient characteristicsTumor characteristicsPrognostic importancePrognostic utilityReclassification index
2019
Frequent 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 decisionPerilesional edema in brain metastases: potential causes and implications for treatment with immune therapy
Tran TT, Mahajan A, Chiang VL, Goldberg SB, Nguyen DX, Jilaveanu LB, Kluger HM. Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy. Journal For ImmunoTherapy Of Cancer 2019, 7: 200. PMID: 31362777, PMCID: PMC6668163, DOI: 10.1186/s40425-019-0684-z.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAntibodies, Monoclonal, HumanizedAntigens, CD34Antineoplastic Agents, ImmunologicalBlood-Brain BarrierBrain EdemaBrain NeoplasmsCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicDrug Administration ScheduleHumansLung NeoplasmsMelanomaRetrospective StudiesTight JunctionsTreatment OutcomeTumor Cells, CulturedConceptsMelanoma brain metastasesBrain metastasesPerilesional edemaVessel densityEdema volumeSensitive tumorsBlood-brain barrier model systemNon-small cell lungTight junction resistancePhase II clinical trialSignificant perilesional edemaUntreated brain metastasesBlood-brain barrierPre-clinical modelsDegree of edemaTumor mass effectPotential causesMelanoma brainShort-term cultureExtracranial metastasesImmune therapyMelanoma patientsSignificant morbidityCell lungLarge tumors
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 progressionBRAF V600 Mutation and BRAF Kinase Inhibitors in Conjunction With Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A Multicenter Retrospective Study
Mastorakos P, Xu Z, Yu J, Hess J, Qian J, Chatrath A, Taylor DG, Kondziolka D, Warnick R, Chiang V, Sheehan J. BRAF V600 Mutation and BRAF Kinase Inhibitors in Conjunction With Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A Multicenter Retrospective Study. Neurosurgery 2018, 84: 868-880. PMID: 29846702, PMCID: PMC6505443, DOI: 10.1093/neuros/nyy203.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesBRAF inhibitorsStereotactic radiosurgeryBRAF mutationsIntracerebral hematomaDiagnosis of BMEffects of BRAFiMulticenter retrospective cohort studyIntracranial melanoma metastasesPD-1 inhibitorsMulticenter retrospective studyRetrospective cohort studyKaplan-Meier methodologyPositive prognostic factorBRAF V600 mutationBRAF mutation statusBRAF kinase inhibitorsMultivariate regression analysisWild-type BRAFCohort studyHazard ratioMedian survivalIndependent predictorsPrognostic factors
2017
Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTLA-4 treatment is associated with improved intracranial control
An Y, Jiang W, Kim BYS, Qian JM, Tang C, Fang P, Logan J, D'Souza NM, Haydu LE, Wang XA, Hess KR, Kluger H, Glitza IC, Mahajan A, Welsh JW, Lin SH, Yu JB, Davies MA, Hwu P, Sulman EP, Brown PD, Chiang VLS, Li J. Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTLA-4 treatment is associated with improved intracranial control. Radiotherapy And Oncology 2017, 125: 80-88. PMID: 28916225, DOI: 10.1016/j.radonc.2017.08.009.Peer-Reviewed Original ResearchConceptsIntracranial disease controlNew brain metastasesIntracranial controlStereotactic radiosurgeryBrain metastasesOverall survivalDisease controlLymphocyte countMulti-institutional retrospective analysisYale-New Haven HospitalMD Anderson cohortMelanoma brain metastasesAbsolute lymphocyte countAntitumor immune responseImmune checkpoint blockadeMetastatic melanoma patientsComplete blood countTumor-specific antigensIndependent validation cohortMulti-institutional studyIpilimumab therapyMedian followLast doseCheckpoint blockadeIntracranial recurrenceCumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases
Hirshman BR, Wilson BR, Ali MA, Schupper AJ, Proudfoot JA, Goetsch SJ, Carter BS, Sinclair G, Bartek J, Chiang V, Fogarty G, Hong A, Chen CC. Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases. Neurosurgery 2017, 83: 237-244. PMID: 28973506, DOI: 10.1093/neuros/nyx380.Peer-Reviewed Original ResearchConceptsCumulative intracranial tumor volumeIntracranial tumor volumeMelanoma brain metastasesBrain metastasesPrognostic valueDS-GPATumor volumeStereotactic radiosurgeryIndependent cohortKey prognostic variablesPrognostic assessment modelPrognostic assessment scaleKarnofsky performance statusNet reclassification indexCerebral metastasesPerformance statusMelanoma patientsPrognostic utilityIntracranial metastasesReclassification indexPrognostic accuracyPrognostic scalesPrognostic variablesPatientsMelanoma cohort
2016
Melanoma 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 ResearchReply to timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery
Yu JB, Chiang VL. Reply to timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 2016, 122: 3577-3578. PMID: 27495789, DOI: 10.1002/cncr.30243.Peer-Reviewed Original ResearchTiming 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 reductionDemonstration of differential radiosensitivity based upon mutation profile in metastatic melanoma treated with stereotactic radiosurgery.
Rutter CE, Johung KL, Yao X, Lu AY, Jilaveanu LB, Yu JB, Contessa JN, Kluger HM, Chiang VLS, Bindra RS. Demonstration of differential radiosensitivity based upon mutation profile in metastatic melanoma treated with stereotactic radiosurgery. Journal Of Radiosurgery And SBRT 2016, 4: 97-106. PMID: 29296434, PMCID: PMC5658871.Peer-Reviewed Original ResearchWild-type patientsC-kit mutationsLocal recurrenceMetastatic melanomaBrain metastasesType patientsN-RASCox proportional hazards modelMelanoma brain metastasesImproved local controlLocal recurrence rateProportional hazards modelN-RAS mutationsB-RafDifferential radiosensitivityDistant failureRecurrence rateImportant treatmentStereotactic radiosurgeryHazards modelPatientsLocal controlMultivariate analysisStandardized imagingRecurrence
2013
Advances 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
2008
Gamma Knife surgery for the treatment of melanoma metastases: the effect of intratumoral hemorrhage on survival.
Redmond AJ, DiLuna ML, Hebert R, Moliterno JA, Desai R, Knisely JP, Chiang VL. Gamma Knife surgery for the treatment of melanoma metastases: the effect of intratumoral hemorrhage on survival. Journal Of Neurosurgery 2008, 109 Suppl: 99-105. PMID: 19123895, DOI: 10.3171/jns/2008/109/12/s16.Peer-Reviewed Original ResearchConceptsGamma Knife surgeryMelanoma metastasesIntratumoral bleedingTime of GKSWhole-brain radiation therapyPost-GKS hemorrhageMelanoma brain metastasesRate of hemorrhageConnecticut Tumor RegistryMalignant melanoma metastaticSurvival of patientsTotal tumor volumeTreatment-specific factorsMelanoma metastaticPosttreatment bleedingAntithrombotic medicationBrain metastasesMetastasis locationOverall survivalSolitary metastasisTumor RegistryTumor burdenWorse prognosisIntracranial metastasesPatient survival