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 ResearchMeSH KeywordsAntineoplastic AgentsBrain NeoplasmsHumansImmunologic FactorsImmunotherapyNeoplasm MetastasisNeoplasm Recurrence, LocalNeurotoxicity SyndromesConceptsBrain 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 teamMetastasisPatients
2018
BRAF 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 ResearchMeSH KeywordsAntineoplastic AgentsBrain NeoplasmsHumansMelanomaMutationPrognosisProtein Kinase InhibitorsProto-Oncogene Proteins B-rafRadiosurgeryRetrospective StudiesConceptsMelanoma 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 factorsEffect of Targeted Therapies on Prognostic Factors, Patterns of Care, and Survival in Patients With Renal Cell Carcinoma and Brain Metastases
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. Effect of Targeted Therapies on Prognostic Factors, Patterns of Care, and Survival in Patients With Renal Cell Carcinoma and Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2018, 101: 845-853. PMID: 29976497, PMCID: PMC6925530, DOI: 10.1016/j.ijrobp.2018.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAngiogenesis InhibitorsAntineoplastic AgentsBrain NeoplasmsCarcinoma, Renal CellCause of DeathCranial IrradiationCytokinesFemaleHemoglobinsHumansImmunotherapyKarnofsky Performance StatusKidney NeoplasmsMaleMiddle AgedMultivariate AnalysisPrognosisRadiosurgeryRetrospective StudiesYoung AdultConceptsPatterns of careNew brain metastasesBrain metastasesLarge contemporary cohortPrognostic factorsMedian survivalContemporary cohortRCC patientsDiagnosis of BMWhole-brain radiation therapyRenal cell carcinoma patientsRetrospective institutional review boardBrain metastasis therapySystemic treatment optionsAdditional prognostic factorsCell carcinoma patientsRenal cell carcinomaInstitutional review boardNonneurologic causesCarcinoma patientsImproved survivalNeurologic causesMultivariable analysisClinical parametersPresent cohort
2017
The Prognostic Value of BRAF, C-KIT, and NRAS Mutations in Melanoma Patients With Brain Metastases
Sperduto PW, Jiang W, Brown PD, Braunstein S, Sneed P, Wattson DA, Shih HA, Bangdiwala A, Shanley R, Lockney NA, Beal K, Lou E, Amatruda T, Sperduto WA, Kirkpatrick JP, Yeh N, Gaspar LE, Molitoris JK, Masucci L, Roberge D, Yu J, Chiang V, Mehta M. The Prognostic Value of BRAF, C-KIT, and NRAS Mutations in Melanoma Patients With Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2017, 98: 1069-1077. PMID: 28721890, PMCID: PMC6925531, DOI: 10.1016/j.ijrobp.2017.03.030.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBrain NeoplasmsFemaleGenes, rasHumansImmunotherapyLinear ModelsMaleMelanomaMiddle AgedMolecular Targeted TherapyMutationPrognosisProportional Hazards ModelsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-kitRetrospective StudiesStatistics, NonparametricTime FactorsConceptsBRAF-negative patientsBRAF-positive patientsBrain metastasesMedian survivalC-kit mutationsMelanoma patientsPrimary diagnosisWhole-brain radiation therapyOverall median survivalMulti-institutional databaseGene mutation statusOverall survivalInitial treatmentMedian timeTreatment patternsClinical parametersBRAF statusPrognostic valueNRAS mutationsRadiation therapyPatientsMutation statusMetastasisC-kitMEK inhibitorsManagement of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis
Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. Journal Of Clinical Oncology 2017, 35: jco.2016.69.714. PMID: 28113019, DOI: 10.1200/jco.2016.69.7144.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungCombined Modality TherapyCranial IrradiationDisease-Free SurvivalErbB ReceptorsErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsRadiosurgeryRetrospective StudiesSalvage TherapySurvival RateConceptsWhole brain radiotherapyMulti-institutional analysisEGFR-mutant NSCLCBrain metastasesEGFR-TKIStereotactic radiosurgeryTyrosine kinase inhibitorsOverall survivalEpidermal growth factor receptorGrowth factor receptorIntracranial progressionLung cancerMutant non-small cell lung cancerEGFR-TKI resistance mutationNon-small cell lung cancerIntracranial progression-free survivalRetrospective multi-institutional analysisDeferral of radiotherapyEGFR-TKI useSimilar prognostic featuresUpfront EGFR-TKIProgression-free survivalFactor receptorInferior overall survivalCell lung cancer
2016
The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases
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. The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2016, 96: 406-413. PMID: 27598807, PMCID: PMC5575932, DOI: 10.1016/j.ijrobp.2016.06.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsErbB ReceptorsFemaleGenetic MarkersGenetic Predisposition to DiseaseHumansIncidenceLung NeoplasmsMaleMiddle AgedMutationPolymorphism, Single NucleotidePrevalenceProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesRetrospective StudiesRisk FactorsSurvival RateUnited StatesConceptsTyrosine kinase inhibitionBrain metastasesMedian survivalCause of deathGene alterationsDiagnosis of BMMulti-institutional retrospective databaseTKI-naïve patientsRisk of deathLonger median survivalKinase inhibitionALK gene alterationsTreatment patternsCancer mortalityLung cancerPrimary diagnosisRetrospective databaseCommon causeLung adenocarcinomaGroup overallPatientsFirst treatmentPrior trialsEGFRMonthsPembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohortPossible 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 changesImmunotherapyMalignancyMelanoma 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 ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBrain NeoplasmsDisease ProgressionFemaleHumansMelanomaMiddle AgedSkin NeoplasmsConceptsCentral 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
Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis
Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, Ning MS, Attia A, Lovly CM, Goldberg S, Beal K, Yu JB, Kavanagh BD, Chiang VL, Camidge DR, Contessa JN. Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis. Journal Of Clinical Oncology 2015, 34: 123-129. PMID: 26438117, PMCID: PMC5070549, DOI: 10.1200/jco.2015.62.0138.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarbazolesCarcinoma, Non-Small-Cell LungCranial IrradiationCrizotinibDisease-Free SurvivalFemaleFollow-Up StudiesGene RearrangementHumansKaplan-Meier EstimateKarnofsky Performance StatusLung NeoplasmsMaleMiddle AgedMolecular Targeted TherapyNeoplasm StagingPiperidinesPrognosisProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyridinesPyrimidinesRadiosurgeryReceptor Protein-Tyrosine KinasesRisk AssessmentRisk FactorsSmokingSulfonesConceptsIntracranial progression-free survivalBrain metastasesProgression-free survivalPrognostic factorsLung cancerMedian intracranial progression-free survivalNon-small cell lung cancerTyrosine kinase inhibitor therapyProgressive brain metastasesRefinement of prognosisKarnofsky performance scorePercent of patientsClinical prognostic factorsPopulation of patientsSingle brain metastasisCell lung cancerKinase inhibitor therapyCox proportional hazardsMulti-institutional studyMedian OSExtracranial metastasesImproved survivalInhibitor therapyInitial treatmentMultivariable analysis
2013
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Johung KL, Yao X, Li F, Yu JB, Gettinger SN, Goldberg S, Decker RH, Hess JA, Chiang VL, Contessa JN. A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer. Clinical Cancer Research 2013, 19: 5523-5532. PMID: 23897899, DOI: 10.1158/1078-0432.ccr-13-0836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsRadiation ToleranceReceptor Protein-Tyrosine KinasesRecurrenceTranslocation, GeneticTumor BurdenConceptsNon-small cell lung cancerCell lung cancerEML4-ALK translocationGamma knife treatmentLocal controlTumor genotypeLung cancerEGFR mutationsCox proportional hazards modelDistant brain controlDistant brain recurrenceGamma knife radiotherapyEGFR kinase domain mutationsSuperior local controlField local controlKRAS mutation statusProportional hazards modelKinase domain mutationsEGF receptorMetastasis sizeBrain recurrenceBrain metastasesField recurrenceClinical outcomesIndependent predictorsAdvances 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