2021
Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases
Lu BY, Gupta R, Aguirre-Ducler A, Gianino N, Wyatt H, Ribeiro M, Chiang VL, Contessa JN, Adeniran AJ, Jilaveanu LB, Kluger HM, Schalper KA, Goldberg SB. Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases. Journal For ImmunoTherapy Of Cancer 2021, 9: e002684. PMID: 34670827, PMCID: PMC8529973, DOI: 10.1136/jitc-2021-002684.Peer-Reviewed Original ResearchConceptsPrimary lung tumorsT cell subsetsMajor T cell subsetsMultiplexed quantitative immunofluorescenceLung tumorsT cellsCoinhibitory receptorsTim-3Cell subsetsBrain metastasesQuantitative immunofluorescenceHigh LAG-3 expressionTumor PD-L1 expressionPD-L1 protein expressionLymphocyte activation gene-3Low T cell infiltrationHigh TIM-3Major clinicopathological variablesPD-L1 expressionLAG-3 expressionT cell infiltrationTumor-infiltrating lymphocytesLonger overall survivalCell death 1Tumor immune microenvironment
2020
Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial
Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Wilson FH, Omay SB, Yu JB, Jilaveanu L, Tran T, Pavlik K, Rowen E, Gerrish H, Komlo A, Gupta R, Wyatt H, Ribeiro M, Kluger Y, Zhou G, Wei W, Chiang VL, Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2020, 21: 655-663. PMID: 32251621, PMCID: PMC7380514, DOI: 10.1016/s1470-2045(20)30111-x.Peer-Reviewed Original ResearchConceptsBrain metastasis responseYale Cancer CenterPD-L1 expressionPhase 2 trialUntreated brain metastasesBrain metastasesAdrenal insufficiencyAdverse eventsMetastasis responseCNS diseaseCancer CenterCohort 2Cohort 1Eastern Cooperative Oncology Group performance statusTreatment-related serious adverse eventsModified Response Evaluation CriteriaStage IV NSCLCTreatment-related deathsAcute kidney injuryPD-1 blockadeSerious adverse eventsSolid Tumors criteriaPhase 2 studyProportion of patientsResponse Evaluation CriteriaEstrogen/progesterone receptor and HER2 discordance between primary tumor and brain metastases in breast cancer and its effect on treatment and survival
Sperduto PW, Mesko S, Li J, Cagney D, Aizer A, Lin NU, Nesbit E, Kruser TJ, Chan J, Braunstein S, Lee J, Kirkpatrick JP, Breen W, Brown PD, Shi D, Shih HA, Soliman H, Sahgal A, Shanley R, Sperduto W, Lou E, Everett A, Boggs DH, Masucci L, Roberge D, Remick J, Plichta K, Buatti JM, Jain S, Gaspar LE, Wu CC, Wang TJC, Bryant J, Chuong M, Yu J, Chiang V, Nakano T, Aoyama H, Mehta MP. Estrogen/progesterone receptor and HER2 discordance between primary tumor and brain metastases in breast cancer and its effect on treatment and survival. Neuro-Oncology 2020, 22: 1359-1367. PMID: 32034917, PMCID: PMC7523450, DOI: 10.1093/neuonc/noaa025.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBrain NeoplasmsBreast NeoplasmsEstrogensHumansReceptor, ErbB-2Receptors, ProgesteroneRetrospective StudiesConceptsBreast cancer brain metastasesHuman epidermal growth factor receptor 2Primary tumorProgesterone receptorMedian survivalEstrogen receptorBrain metastasesDiscordance rateHER2-negative primary tumorsEstrogen/progesterone receptorsEpidermal growth factor receptor 2Time of metastasisCancer brain metastasesGrowth factor receptor 2Breast cancer treatmentIncidence of discordanceFactor receptor 2Subsequent treatmentBCBM patientsHER2 discordanceReceptor discordanceMost patientsReceptor statusInitial diagnosisHER2 status
2019
Transcriptomic 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 cellsHallmarkTranscriptomeCells
2018
Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool
Sperduto PW, Deegan BJ, Li J, Jethwa KR, Brown PD, Lockney N, Beal K, Rana NG, Attia A, Tseng CL, Sahgal A, Shanley R, Sperduto WA, Lou E, Zahra A, Buatti JM, Yu JB, Chiang V, Molitoris JK, Masucci L, Roberge D, Shi DD, Shih HA, Olson A, Kirkpatrick JP, Braunstein S, Sneed P, Mehta MP. Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool. Neuro-Oncology 2018, 20: 1652-1660. PMID: 30418657, PMCID: PMC6231200, DOI: 10.1093/neuonc/noy099.Peer-Reviewed Original ResearchConceptsPrognostic assessment toolsBrain metastasesRenal cell carcinomaMedian survivalPrognostic factorsAdditional significant prognostic factorsRenal cell carcinoma patientsRetrospective institutional review boardNew brain metastasesKarnofsky performance statusOverall median survivalCell carcinoma patientsSignificant prognostic factorsFuture clinical trialsClinical decision makingInstitutional review boardAssessment toolPerformance statusCommon complicationExtracranial metastasesHazard ratioCarcinoma patientsContemporary cohortRCC patientsWorse prognosis
2017
Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study
Kaidar-Person O, Meattini I, Jain P, Bult P, Simone N, Kindts I, Steffens R, Weltens C, Navarria P, Belkacemi Y, Lopez-Guerra J, Livi L, Baumert B, Vieites B, Limon D, Kurman N, Ko K, Yu J, Chiang V, Poortmans P, Zagar T. Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study. Breast Cancer Research And Treatment 2017, 167: 479-483. PMID: 28975433, DOI: 10.1007/s10549-017-4526-8.Peer-Reviewed Original ResearchConceptsBreast cancer patientsSubsequent brain metastasesHuman epidermal growth factor receptor 2Brain metastasesCancer patientsEthical research committeeReceptor statusPrimary tumorProgesterone receptorEstrogen receptorEpidermal growth factor receptor 2Triple-negative profileGrowth factor receptor 2Primary breast cancerPrimary breast tumorsInternational multicenter studyFactor receptor 2Multicenter studyAvailable histologyResultsA totalBreast cancerReceptor 2ConclusionsThe majorityPatientsBreast tumorsEstimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)
Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, Shanley R, Yeh N, Gaspar LE, Braunstein S, Sneed P, Boyle J, Kirkpatrick JP, Mak KS, Shih HA, Engelman A, Roberge D, Arvold ND, Alexander B, Awad MM, Contessa J, Chiang V, Hardie J, Ma D, Lou E, Sperduto W, Mehta MP. Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA). JAMA Oncology 2017, 3: 827-831. PMID: 27892978, PMCID: PMC5824323, DOI: 10.1001/jamaoncol.2016.3834.Peer-Reviewed Original ResearchConceptsDiagnosis-Specific Graded Prognostic AssessmentBrain metastasesGraded Prognostic AssessmentFuture clinical trialsLung cancerLung-molGPAMedian survivalPrognostic factorsHazard ratioClinical trialsMAIN OUTCOMEPrognostic assessmentLung-molGPA scoreOverall median survivalKarnofsky performance statusMultiple Cox regressionSignificant prognostic factorsCell lung cancerRetrospective database analysisCancer-related mortalityLog-rank testHeterogeneous patient populationClinical decision makingExtracranial metastasesOverall survival
2015
Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites
Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, Rimm DL, Chen L, Jilaveanu LB. Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites. Clinical Cancer Research 2015, 21: 3052-3060. PMID: 25788491, PMCID: PMC4490112, DOI: 10.1158/1078-0432.ccr-14-3073.Peer-Reviewed Original ResearchConceptsPD-L1 expressionT-cell contentPD-1/PD-L1 inhibitorsHigher T-cell contentT-cell infiltratesPD-L1 inhibitorsAnatomic sitesBrain metastasesMetastatic melanomaTissue microarrayHigh PD-L1 expressionLess PD-L1 expressionLow PD-L1 expressionTumor PD-L1 expressionHigher TIL contentImproved overall survivalT cell infiltrationLess T cellsMetastatic melanoma samplesExtracerebral metastasesCerebral metastasesOverall survivalDermal metastasesImproved survivalPD-L1