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 effectsMetastasisRadiotherapyResectionOutcomes of Stereotactic Radiosurgery and Immunotherapy in Renal Cell Carcinoma Patients With Brain Metastases
Uezono H, Nam D, Kluger HM, Sznol M, Hurwitz M, Yu JB, Chiang VL. Outcomes of Stereotactic Radiosurgery and Immunotherapy in Renal Cell Carcinoma Patients With Brain Metastases. American Journal Of Clinical Oncology 2021, 44: 495-501. PMID: 34432667, DOI: 10.1097/coc.0000000000000849.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRCC brain metastasesBrain metastasesRenal cell carcinomaStereotactic radiosurgeryOverall survivalUse of ICIsCentral nervous system toxicityRenal cell carcinoma patientsImpact of immunotherapyLocal control outcomesMedian overall survivalCell carcinoma patientsKaplan-Meier curvesNervous system toxicityBetter median OSLog-rank testMann-Whitney U testMargin doseMedian OSNonimmunotherapy groupSRS doseCheckpoint inhibitorsImmunotherapy groupCarcinoma patients
2020
Systemic 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 inhibitionMelanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy
Margolin K, Davies M, Kluger H, Tawbi H. Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy. 2020, 1421-1454. DOI: 10.1007/978-3-030-05070-2_65.Peer-Reviewed Original ResearchMelanoma brain metastasesCentral nervous systemSystemic therapyClinical benefitMainstay of therapyUnique patient populationDuration of responseHigh response rateFuture drug developmentMelanoma metastaticBrain metastasesDevastating complicationDurable responsesImmune checkpointsImmune therapyPatient populationMetastatic melanomaEffective modalityStereotactic radiosurgeryNervous systemResponse rateTherapyMultidisciplinary approachDrug developmentMelanoma[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
Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy
Margolin K, Davies M, Kluger H, Tawbi H. Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy. 2019, 1-34. DOI: 10.1007/978-3-319-46029-1_65-1.Peer-Reviewed Original ResearchMelanoma brain metastasesCentral nervous systemSystemic therapyClinical benefitMainstay of therapyUnique patient populationDuration of responseHigh response rateFuture drug developmentMelanoma metastaticBrain metastasesDevastating complicationDurable responsesImmune checkpointsImmune therapyPatient populationMetastatic melanomaEffective modalityStereotactic radiosurgeryNervous systemResponse rateTherapyMultidisciplinary approachDrug developmentMelanoma
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 recurrence
2016
The 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 interventionTiming 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 reductionPossible 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 changesImmunotherapyMalignancyDemonstration 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
2015
Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?
Colaco RJ, Martin P, Kluger HM, Yu JB, Chiang VL. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? Journal Of Neurosurgery 2015, 125: 17-23. PMID: 26544782, DOI: 10.3171/2015.6.jns142763.Peer-Reviewed Original ResearchConceptsTreatment-related imaging changesCytotoxic chemotherapyRadiation necrosisBrain metastasesSystemic therapyStereotactic Gamma Knife radiosurgeryMedian overall survivalGamma knife radiosurgeryHigh-dose radiationChemotherapy eraGK surgeryImmunotherapy increasesMedian followConclusions PatientsOverall survivalImaging changesGK treatmentKnife radiosurgeryInflammatory reactionStereotactic radiosurgeryLower riskRadiosurgical treatmentPatientsImmunotherapyTherapy