2021
Outcomes 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
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 ResearchConceptsBrain 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 teamMetastasisPatientsFrequent 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 decisionLocal tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non-small cell lung cancer with brain metastases.
Singh C, Qian JM, Yu JB, Chiang VL. Local tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non-small cell lung cancer with brain metastases. Journal Of Neurosurgery 2019, 132: 512-517. PMID: 30771783, DOI: 10.3171/2018.10.jns181371.Peer-Reviewed Original ResearchConceptsAnti-PD-1 therapyKarnofsky performance statusBrain metastasesLung cancer patientsStereotactic radiosurgeryCT groupIT groupCancer patientsNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsAntibody-positive patientsGraded Prognostic AssessmentCox regression analysisCell lung cancerMedian survival timeLocal tumor responseWhole study groupMann-Whitney U testTerms of survivalLesional responseMedian survivalPerformance statusWorse survivalComplete response
2018
Effect 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 inhibitorsComparing available criteria for measuring brain metastasis response to immunotherapy
Qian JM, Mahajan A, Yu JB, Tsiouris AJ, Goldberg SB, Kluger HM, Chiang VL. Comparing available criteria for measuring brain metastasis response to immunotherapy. Journal Of Neuro-Oncology 2017, 132: 479-485. PMID: 28275886, DOI: 10.1007/s11060-017-2398-8.Peer-Reviewed Original ResearchConceptsRECIST 1.1Brain lesionsBrain metastasesDurable responsesAdditional patientsNeuro-Oncology Working GroupBrain metastasis responseBrain metastasis patientsUntreated brain metastasesStandardized response criteriaBrain lesion sizeHigh-grade gliomasSimilar clinical trialsHigh-resolution MRIMetastasis patientsMetastasis responseOngoing trialsClinical trialsNovel therapiesResponse assessmentDiscordant casesLesion sizePatientsResponse rateLongest diameter
2016
Timing 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 changesImmunotherapyMalignancy
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 treatmentPatientsImmunotherapyTherapyClinical trials in melanoma patients with brain metastases
Yushak ML, Chiang VL, Kluger HM. Clinical trials in melanoma patients with brain metastases. Pigment Cell & Melanoma Research 2015, 28: 741-743. PMID: 26205399, PMCID: PMC4834841, DOI: 10.1111/pcmr.12401.Peer-Reviewed Original Research