2020
Melanoma 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 trialsSurvival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma
Klemen ND, Wang M, Rubinstein JC, Olino K, Clune J, Ariyan S, Cha C, Weiss SA, Kluger HM, Sznol M. Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma. Journal For ImmunoTherapy Of Cancer 2020, 8: e000341. PMID: 32209601, PMCID: PMC7103823, DOI: 10.1136/jitc-2019-000341.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsOverall survivalMetastatic melanomaPrimary tumorLocal therapyCutaneous melanomaAnti-PD-1 antibodyAggressive multidisciplinary approachCutaneous primary tumorPrimary tumor histologyMedian overall survivalSingle institutional experienceRare melanoma subtypeMedian OSMetastatic diseaseProgressive diseaseAcral skinComplete responsePD-1PD-L1Uveal tractTumor histologyCombination therapyCTLA-4Longer survival
2019
Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease
Abu-Sbeih H, Faleck DM, Ricciuti B, Mendelsohn RB, Naqash AR, Cohen JV, Sellers MC, Balaji A, Ben-Betzalel G, Hajir I, Zhang J, Awad MM, Leonardi GC, Johnson DB, Pinato DJ, Owen DH, Weiss SA, Lamberti G, Lythgoe MP, Manuzzi L, Arnold C, Qiao W, Naidoo J, Markel G, Powell N, Yeung SJ, Sharon E, Dougan M, Wang Y. Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease. Journal Of Clinical Oncology 2019, 38: 576-583. PMID: 31800340, PMCID: PMC7030892, DOI: 10.1200/jco.19.01674.Peer-Reviewed Original ResearchConceptsGI adverse eventsInflammatory bowel diseaseImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyImmune checkpoint inhibitorsAdverse eventsCheckpoint inhibitorsBowel diseaseInhibitor therapyAnti-cytotoxic T-lymphocyte antigen-4 therapyTreatment of IBDCytotoxic T-lymphocyte antigen-4T-lymphocyte antigen-4Cell death 1Multivariate logistic regressionImmunotherapy initiationColonic perforationGI eventsDeath-1Ulcerative colitisCrohn's diseaseMedian timeMultivariable analysisRetrospective studySimilar patientsPLEKHA5 regulates tumor growth in metastatic melanoma
Zhang H, Zhu H, Deng G, Zito CR, Oria VO, Rane CK, Zhang S, Weiss SA, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg MW, Kluger HM, Jilaveanu LB. PLEKHA5 regulates tumor growth in metastatic melanoma. Cancer 2019, 126: 1016-1030. PMID: 31769872, PMCID: PMC7147081, DOI: 10.1002/cncr.32611.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsApoptosis Regulatory ProteinsBiomarkers, TumorBrain NeoplasmsCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, NudeMiddle AgedPhosphatidylinositol 3-KinasesPrognosisProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesTumor Cells, CulturedXenograft Model Antitumor AssaysYoung AdultConceptsTumor growthDisseminated melanomaExtracranial melanoma metastasesPI3K/AKT/mTOR pathwayMelanoma brain metastasesBetter overall survivalPI3K/Akt/mTORAKT/mTOR pathwayCell proliferationAkt/mTORMelanoma xenograft modelGrowth of tumorsS cell cycle transitionBrain metastasesOverall survivalPoor prognosisMetastatic melanomaMAPK/ERKSubcutaneous inoculationMelanoma metastasesXenograft modelClinical relevanceMelanoma growthNude miceCerebral specimensPatterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma
Klemen ND, Wang M, Feingold PL, Cooper K, Pavri SN, Han D, Detterbeck FC, Boffa DJ, Khan SA, Olino K, Clune J, Ariyan S, Salem RR, Weiss SA, Kluger HM, Sznol M, Cha C. Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 196. PMID: 31340861, PMCID: PMC6657062, DOI: 10.1186/s40425-019-0672-3.Peer-Reviewed Original ResearchConceptsThree-year progression-free survivalProgression-free survivalDisease-specific survivalFive-year disease-specific survivalPatterns of failureDurable progression-free survivalLocal therapyStereotactic body radiotherapyMetastatic melanomaNew metastasesPatient selectionIndependent radiological reviewOngoing complete responseResultsFour hundred twentyEvidence of diseaseCNS metastasisCPI treatmentImmunotherapy failureCheckpoint inhibitorsMost patientsProgressive diseaseRadiological reviewComplete responsePD-1PD-L1Ophthalmic Immune-Related Adverse Events of Immunotherapy: A Single-Site Case Series
Kim J, Materin MA, Sznol M, Kluger H, Weiss S, Chow J, Stoessel K, Kombo N, Del Priore L, Pointdujour-Lim R. Ophthalmic Immune-Related Adverse Events of Immunotherapy: A Single-Site Case Series. Ophthalmology 2019, 126: 1058-1062. PMID: 30735682, PMCID: PMC6933747, DOI: 10.1016/j.ophtha.2019.01.031.Peer-Reviewed Original Research
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 progressionTumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805
Jilaveanu LB, Puligandla M, Weiss SA, Wang X, Zito C, Flaherty KT, Boeke M, Neumeister V, Camp RL, Adeniran A, Pins M, Manola J, DiPaola RS, Haas N, Kluger HM. Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805. Clinical Cancer Research 2018, 24: 217-223. PMID: 29066509, PMCID: PMC5904512, DOI: 10.1158/1078-0432.ccr-17-1555.Peer-Reviewed Original ResearchConceptsHigher microvessel densityDisease-free survivalRenal cell carcinomaHigh-risk RCC patientsImproved overall survivalOverall survivalMicrovessel densityRCC patientsAdjuvant therapy trialsClear cell histologyHigh-risk patientsBiomarkers of outcomeTumor microvessel densityLower microvessel densityAbsence of necrosisFuhrman grade 1Clin Cancer ResAdjuvant sunitinibProlonged OSCell histologyLymphovascular invasionSarcomatoid featuresMultivariable analysisTreatment armsEntire cohort
2017
Treatment Outcomes for Metastatic Melanoma of Unknown Primary in the New Era: A Single-Institution Study and Review of the Literature
Utter K, Goldman C, Weiss SA, Shapiro RL, Berman RS, Wilson MA, Pavlick AC, Osman I. Treatment Outcomes for Metastatic Melanoma of Unknown Primary in the New Era: A Single-Institution Study and Review of the Literature. Oncology 2017, 93: 249-258. PMID: 28746931, PMCID: PMC5617794, DOI: 10.1159/000478050.Peer-Reviewed Original ResearchConceptsMUP patientsProspective melanoma databaseSystemic therapyUnknown primaryMetastatic melanomaClinical trialsSingle-institution studyMKP patientsTreatment guidelinesPoor outcomeMelanoma databaseWorse outcomesTreatment outcomesPatientsBetter outcomesTherapyPatient dataMelanomaGoogle ScholarUnique populationSurvival dataOutcomesLimited dataImmunotherapyTrials
2016
Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts
Weiss SA, Han J, Darvishian F, Tchack J, Han SW, Malecek K, Krogsgaard M, Osman I, Zhong J. Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts. Journal Of Translational Medicine 2016, 14: 299. PMID: 27760559, PMCID: PMC5070187, DOI: 10.1186/s12967-016-1026-2.Peer-Reviewed Original ResearchConceptsMelanoma-specific survivalShorter melanoma-specific survivalHost immune responseImmune responseTCGA cohortAge groupsClinicopathologic featuresSurvival outcomesPatient cohortPrimary melanomaHost anti-tumor immune responseMelanoma diagnosisAnti-tumor immune responseMelanoma Cooperative GroupIndependent prognostic factorPopulation-based surveillanceEnd Results ProgramGreater prognostic impactMelanoma patient cohortTop upstream regulatorsYounger age groupsAge-related factorsBrisk TILsConclusionsOlder ageLymphocyte measurementsImmunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma
Weiss SA, Han SW, Lui K, Tchack J, Shapiro R, Berman R, Zhong J, Krogsgaard M, Osman I, Darvishian F. Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma. Human Pathology 2016, 57: 116-125. PMID: 27473267, PMCID: PMC5706446, DOI: 10.1016/j.humpath.2016.07.008.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkers, TumorCD3 ComplexDisease-Free SurvivalFemaleForkhead Transcription FactorsGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLeukocyte Common AntigensLymphocytes, Tumor-InfiltratingMaleMelanomaNeoplasm GradingPhenotypeProportional Hazards ModelsSkin NeoplasmsTime FactorsTreatment OutcomeConceptsAbsent tumor-infiltrating lymphocytesTumor-infiltrating lymphocytesBrisk tumor-infiltrating lymphocytesRecurrence-free survivalPrimary melanomaTIL gradeOverall survivalImmunologic heterogeneityPresence of TILsHost antitumor immune responseAntitumor immune responseImmune checkpoint regulatorsLymphocyte markers CD3T cell activation pathwaysEosin-stained sectionsGene expression profilesIndependent prognosticationLymphocyte compositionTIL countSurvival outcomesImproved prognosisPrognostic valueHistologic evaluationNonbriskImmune response
2015
Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis
Weiss S, Darvishian F, Tadepalli J, Shapiro R, Golfinos J, Pavlick A, Polsky D, Kirchhoff T, Osman I. Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis. BMC Cancer 2015, 15: 926. PMID: 26597176, PMCID: PMC4657192, DOI: 10.1186/s12885-015-1927-0.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesRecurrent brain metastasesBrain metastasesOverall survivalLong-term melanoma survivorsSingle nucleotide polymorphismsYear old manIndividual patient's tumorGenetic variantsMelanoma patientsMelanoma survivorsPrognostic informationFavorable outcomeNRAS wild typePatient outcomesConclusionsOur dataPatient tumorsImmune functionBrain tumorsExtended survivalOlder menPatientsClinical scenariosGermline analysisTherapeutic interventions