2025
Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.
Weiss S, Djureinovic D, Wei W, Tran T, Austin M, Markowitz J, Eroglu Z, Khushalani N, Hegde U, Cohen J, Sznol M, Anderson G, Johnson B, Piteo C, Mahajan A, Adeniran A, Jilaveanu L, Goldberg S, Chiang V, Forsyth P, Kluger H. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases. Journal Of Clinical Oncology 2025, jco2402219. PMID: 40048689, DOI: 10.1200/jco-24-02219.Peer-Reviewed Original ResearchMelanoma brain metastasesOverall survivalBrain metastasesAnti-vascular endothelial growth factor therapyMedian intracranial progression-free survivalFour-year OS ratesIntracranial progression-free survivalResponse rateCirculating angiopoietin-2Median overall survivalTrial of pembrolizumabYears of pembrolizumabDose of bevacizumabProgression-free survivalPhase II trialGrowth factor therapyAdverse event ratesAssociated with responseOS ratesPD-1Radiation necrosisLocal therapyOn-therapyMetastatic tumorsFactor therapySurvival of patients with metastatic renal cell carcinoma with or without brain metastases.
Hurwitz M, Considine B, Hasson N, Savion Gaiger N, Nelson M, Chiang V, Kluger H, Braun D, Schoenfeld D, Sznol M, Leapman M. Survival of patients with metastatic renal cell carcinoma with or without brain metastases. Journal Of Clinical Oncology 2025, 43: 476-476. DOI: 10.1200/jco.2025.43.5_suppl.476.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsClear cell RCCRenal cell carcinomaImmune checkpoint inhibitor therapyMetastatic clear cell RCCBrain metastasesOverall survivalCell carcinomaImmune checkpoint inhibitor eraPrevalence of brain metastasesMultivariate Cox proportional hazards modelAssociated with poor survivalMedian overall survivalAssociated with poor prognosisCompare overall survivalImproved overall survivalAdverse prognostic indicatorDevelopment of BMSurvival of patientsKaplan-Meier analysisYale Cancer CenterRetrospective cohort studyCox proportional hazards modelsProportional hazards model
2024
RADT-45. INTEGRATION OF FUNCTIONAL MAGNETIC RESONANCE IMAGING INTO STEREOTACTIC RADIOSURGERY PLANNING TO REDUCE SYMPTOMATIC RADIATION NECROSIS
Gui C, Jenabi M, Daly J, Gillick C, Bradley T, Sze E, Maldonado R, Tiwari A, Stember J, Mankuzhy N, Yamada Y, Pike L, Pasquini L, Peck K, Ballangrud-Popovic Å, Holodny A, Imber B. RADT-45. INTEGRATION OF FUNCTIONAL MAGNETIC RESONANCE IMAGING INTO STEREOTACTIC RADIOSURGERY PLANNING TO REDUCE SYMPTOMATIC RADIATION NECROSIS. Neuro-Oncology 2024, 26: viii83-viii83. PMCID: PMC11554023, DOI: 10.1093/neuonc/noae165.0329.Peer-Reviewed Original ResearchStereotactic radiosurgerySymptomatic RNRadiation necrosisBrain metastasesNeurological symptomsDosimetric analysisTarget coverageComplications of stereotactic radiosurgeryMonths of SRSSacrificing target coverageSymptomatic radiation necrosisUnresectable brain metastasesMonths post-SRSEloquent cortical areasFunctional magnetic resonance imagingFocal neurological symptomsMagnetic resonance imagingRadiosurgery planningPost-SRSSRS plansPrimary motorEloquent areasNeurological functionPatientsResonance imagingClinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma
Dunne E, Fick C, Mastrogiacomo B, Tan K, Toumbacaris N, Vanstraelen S, Rocco G, Chaft J, Iyengar P, Gomez D, Adusumilli P, Park B, Isbell J, Bott M, Sihag S, Molena D, Huang J, Jones D. Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma. JTCVS Open 2024, 22: 458-469. PMID: 39780816, PMCID: PMC11704575, DOI: 10.1016/j.xjon.2024.09.030.Peer-Reviewed Original ResearchResection of lung adenocarcinomaMaximum standardized uptake valueDevelopment of brain metastasesBrain metastasesStandardized uptake valueNeoadjuvant therapyLung adenocarcinomaAssociated with developmentLymphovascular invasionTP53 mutationsUptake valueCumulative incidence of brain metastasesMarker of aggressive tumor biologyHighest maximum standardized uptake valueLack of extracranial metastasesIncidence of brain metastasesNext-generation sequencingPanel next-generation sequencingAssociated with better survivalStage III diseaseMedian follow-upAggressive tumor biologyBetter performance statusAssociated with brain metastasisStereotactic radiosurgeryP10.25.A STANDARDIZATION AND AUTOMATIZATION OF MEASURING AND REPORTING BRAIN METASTASIS OVER TIME BY LEVERAGING ARTIFICIAL INTELLIGENCE
Weiss D, Bousabarah K, Deuschl C, Chadha S, Ashraf N, Ramakrishnan D, Moawad A, Osenberg K, Schoenherr S, Lautenschlager J, Holler W, Westerhoff M, Schrickel E, Memon F, Moily N, Malhotra A, Lin M, Aboian M. P10.25.A STANDARDIZATION AND AUTOMATIZATION OF MEASURING AND REPORTING BRAIN METASTASIS OVER TIME BY LEVERAGING ARTIFICIAL INTELLIGENCE. Neuro-Oncology 2024, 26: v61-v61. PMCID: PMC11485790, DOI: 10.1093/neuonc/noae144.201.Peer-Reviewed Original ResearchReports of brain metastasesBrain metastasesInter-observer variabilityFollow-up imaging of patientsPost-Gamma knife radiosurgeryBrain tumorsRANO-BM criteriaFollow-up imagingBoard-certified neuroradiologistsTreatment response monitoringMean Dice coefficientImages of patientsNnU-Net segmentationManual diameter measurementsBM evaluationRANO-BMRetrospective studyTreatment regimenSpearman correlation coefficientInter-rater variabilityMRI reportsIdentified lesionsPercentual changePost-gammaNeuroradiologistsPre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates
Jansen C, Pagadala M, Cardenas M, Prabhu R, Goyal S, Zhou C, Chappa P, Vo B, Ye C, Hopkins B, Zhong J, Klie A, Daniels T, Admassu M, Green I, Pfister N, Neill S, Switchenko J, Prokhnevska N, Hoang K, Torres M, Logan S, Olson J, Nduom E, del Balzo L, Patel K, Burri S, Asher A, Wilkinson S, Lake R, Kesarwala A, Higgins K, Patel P, Dhere V, Sowalsky A, Carter H, Khan M, Kissick H, Buchwald Z. Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates. Nature Communications 2024, 15: 8854. PMID: 39402027, PMCID: PMC11473782, DOI: 10.1038/s41467-024-53034-6.Peer-Reviewed Original ResearchConceptsPre-operative stereotactic radiosurgeryCD8 T cellsEffector-like cellsT cellsStereotactic radiosurgeryBrain metastasesCD8 T cell responsesEndpoint of overall survivalDistant brain failureResected brain metastasesEfficacy of immunotherapyT cell responsesAntigen presenting cellsSecondary clinical endpointsLocal recurrenceLeptomeningeal diseaseOverall survivalImmune compositionProspective trialsImmune nichePrimary endpointImmunological correlatesPresenting cellsClinical outcomesPilot studySequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.
Ascierto P, Mandalà M, Ferrucci P, Guidoboni M, Rutkowski P, Ferraresi V, Arance A, Guida M, Maiello E, Gogas H, Richtig E, Quaglino P, Lebbé C, Helgadottir H, Queirolo P, Spagnolo F, Tucci M, Del Vecchio M, Gonzalez-Cao M, Minisini A, De Placido S, Sanmamed M, Casula M, Bulgarelli J, Pisano M, Piccinini C, Piccin L, Cossu A, Mallardo D, Paone M, Vitale M, Melero I, Grimaldi A, Giannarelli D, Palmieri G, Dummer R, Sileni V. Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma. NEJM Evidence 2024, 3: evidoa2400087. PMID: 39315864, DOI: 10.1056/evidoa2400087.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionBrain metastasesBRAF/MEK inhibitorsArm BArm AProgressive diseaseCheckpoint inhibitionBrain metastases-free survivalImmune checkpoint inhibitor ipilimumabMetastases-free survival ratesDevelopment of brain metastasesCheckpoint inhibitor ipilimumabMetastases-free survivalUnresectable metastatic melanomaV600-mutant melanomaCheckpoint inhibitorsInhibitor ipilimumabMetastatic melanomaBRAF/MEK inhibitionArm CReviewed patientsBRAF/MEKThree-arm trialEncorafenibFollow-upA pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases
André F, Cortés J, Curigliano G, Modi S, Li W, Park Y, Chung W, Kim S, Yamashita T, Pedrini J, Im S, Tseng L, Harbeck N, Krop I, Nakatani S, Tecson K, Ashfaque S, Egorov A, Hurvitz S. A pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases. Annals Of Oncology 2024, 35: 1169-1180. PMID: 39241960, DOI: 10.1016/j.annonc.2024.08.2347.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerBlinded independent central reviewMetastatic breast cancerBrain metastasesT-DXdOverall survivalCNS-PFSTrastuzumab deruxtecanBreast cancerCentral nervous system progression-free survivalIntracranial responsePooled analysisIntracranial objective response rateSafety of trastuzumab deruxtecanSystemic progression-free survivalObjective response rateORR of patientsProgression-free survivalDuration of responseFood and Drug Administration criteriaIndependent central reviewUS Food and Drug Administration criteriaCompare treatmentsExploratory pooled analysisBM statusA Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer
Giordano A, Kumthekar P, Jin Q, Kurt B, Ren S, Li T, Leone J, Mittendorf E, Pereslete A, Sharp L, Davis R, DiLullo M, Tayob N, Mayer E, Winer E, Tolaney S, Lin N. A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39226397, PMCID: PMC11528201, DOI: 10.1158/1078-0432.ccr-24-1161.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesClinical benefit rateCancer brain metastasesCentral nervous systemCNS responseBrain metastasesOverall response rateOverall survivalAny-grade adverse eventsEffective systemic therapy optionsNeuro-Oncology Brain MetastasesHER2-positive breast cancerIntracranial partial responseSystemic therapy optionsPhase II studyPhase II trialCNS ORRRANO-BMDose delaysPartial responseII studyPrimary endpointHigh-doseBenefit rateAnalysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival
Pereslete A, Hughes M, Martin A, Files J, Nguyen K, Buckley L, Patel A, Moore A, Winer E, Dillon D, Li T, Tolaney S, Lin N, Sammons S. Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival. Neuro-Oncology 2024, 27: 184-194. PMID: 39211994, PMCID: PMC11726339, DOI: 10.1093/neuonc/noae163.Peer-Reviewed Original ResearchHER2-low expressionHER2-lowMetastatic breast cancerHER2-positiveHER2 expressionHER2-0Primary tumorBrain metastasesEstrogen receptorBreast cancerHER2-positive primary tumorsASCO-CAP guidelinesNCI-designated centersMultivariate survival analysisCox proportional hazards modelsAntibody-drug conjugatesProportional hazards modelActive antibody-drug conjugateASCO-CAPHER2 gainHER2 statusInferior survivalOverall survivalIntracranial activityRetrospective analysisNIRL-12 UNDERSTANDING LESION RESPONSE ON MRI AFTER LASER INTERSTITIAL THERMAL THERAPY (LITT) IN METASTATIC BRAIN TUMOR PATIENTS
Robert S, Sirota M, Sotoudeh S, Kaur M, Merkaj S, Aboian M, Chiang V. NIRL-12 UNDERSTANDING LESION RESPONSE ON MRI AFTER LASER INTERSTITIAL THERMAL THERAPY (LITT) IN METASTATIC BRAIN TUMOR PATIENTS. Neuro-Oncology Advances 2024, 6: i22-i22. PMCID: PMC11296850, DOI: 10.1093/noajnl/vdae090.073.Peer-Reviewed Original ResearchLaser interstitial thermal therapyPost-LITTPercentage volume changeStereotactic radiosurgeryLesion volumeFLAIR signal abnormalityEnhancing lesion volumeContrast-enhancing lesionsThermal therapyTreatment factorsFLAIR changesImmunotherapy useBrain metastasesPerilesional edemaBiopsy pathologyFLAIR volumeSignal abnormalitiesPatientsLesion changesLesionsMonthsTreatment variablesTherapyFLAIRImaging changesTyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)
Pike L, Miao E, Boe L, Patil T, Imber B, Myall N, Pollom E, Hui C, Qu V, Langston J, Chiang V, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Braunstein S, Kavanagh B, Camidge D, Rusthoven C. Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 3606-3617. PMID: 39047224, PMCID: PMC11874932, DOI: 10.1200/jco.23.02668.Peer-Reviewed Original ResearchNon-small cell lung cancerUp-front stereotactic radiosurgeryTyrosine kinase inhibitorsALK-driven NSCLCStereotactic radiosurgeryBrain metastasesCell lung cancerOverall survivalCNS controlLung cancerOncogene-driven non-small cell lung cancerKinase inhibitorsCNS progression-free survivalStereotactic radiosurgery groupTKI-naive patientsProgression-free survivalAnaplastic lymphoma kinaseEpidermal growth factor receptorCox proportional hazards modelsGrowth factor receptorClinically relevant factorsProportional hazards modelMedian OSNo significant differenceNeurological symptomsPatterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 169: 555-561. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective studyKROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC.
Gregorc V, González-Cao M, Salvagni S, Koumarianou A, Gil-Bazo I, Maio M, Viteri S, Majem M, Gutiérrez V, Bernabe Caro R, Sanmamed M, Zhu H, Shen H, Wang Y, Rosell R. KROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC. Journal Of Clinical Oncology 2024, 42: lba8511-lba8511. DOI: 10.1200/jco.2024.42.17_suppl.lba8511.Peer-Reviewed Original ResearchTreatment-related adverse eventsDisease control ratePhase II studyEpidermal growth factor receptorKRAS G12C inhibitorsDose reduction/interruptionBrain metastasesII studySafety profileG12C inhibitorsBaseline PD-L1 expressionBaseline brain metastasesActivation of epidermal growth factor receptorPD-L1 expressionTreating NSCLC patientsAnti-EGFR antibodiesFront-line treatmentKRAS G12C mutationGrowth factor receptorNSCLC ptsNSCLC modelsTumor shrinkageFrontline therapyNSCLC patientsOpen-labelNavigating the Complexities of Brain Metastases Management.
Amouzegar A, Haig S, Kahn A, Tawbi H, Jones J, Goldberg S. Navigating the Complexities of Brain Metastases Management. American Society Of Clinical Oncology Educational Book 2024, 44: e433694. PMID: 38781565, DOI: 10.1200/edbk_433694.Peer-Reviewed Original ResearchConceptsBrain metastasesSystemic therapySolid tumorsIncidence of brain metastasesManagement of brain metastasesEfficacy of systemic therapyBrain metastasis managementMetastatic solid tumorsComplication of advanced cancerExclusion of patientsEnhanced imaging technologiesMetastasis managementSystemic treatmentTargeted therapyBreast cancerExtended survivalClinical dataClinical trialsMetastasisAdvanced cancerTherapyEarly detectionTumorPatientsCancerNeuro-oncologic Emergencies
Maciel C, Busl K. Neuro-oncologic Emergencies. CONTINUUM Lifelong Learning In Neurology 2024, 30: 845-877. PMID: 38830073, DOI: 10.1212/con.0000000000001435.Peer-Reviewed Original ResearchConceptsNeuro-oncologic emergenciesNeurological complicationsCentral nervous system malignanciesPrimary central nervous system malignancySystemic disease progressionTumor-specific characteristicsAcute neurologic complicationsNervous system malignanciesTreatment-resistant seizuresCSF flow dynamicsIntracranial burdenTumor-mediatedBrain metastasesImmunological therapiesNeuronal hyperexcitabilitySystem malignanciesTumor-relatedNeurotoxicity syndromeIntracranial hypertensionRisk stratificationFavorable outcomeTreatment-relatedSystem cancersDisease progressionComplicationsHLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Vilariño N, Lopez De Rodas M, Ranjan K, Costantini A, Villalba M, Lu B, Kravitz C, Nadal E, Goldberg S, Nguyen D, Schalper K. HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases. Journal Of Clinical Oncology 2024, 42: e14014-e14014. DOI: 10.1200/jco.2024.42.16_suppl.e14014.Peer-Reviewed Original ResearchLung cancer brain metastasisPrimary lung tumorsTumor-infiltrating lymphocytesImmune checkpoint inhibitorsCancer brain metastasesAntigen presentation machineryB2M expressionIFN-gBrain metastasesB2MImmune evasionAssociated with shorter overall survivalMultiplexed quantitative immunofluorescenceM expressionExpression of B2MB2M levelsExpression of pSTAT1Shorter overall survivalUnfavorable clinical featuresNo significant associationAssociated with unfavorable clinical featuresCheckpoint inhibitorsImmunotherapy resistanceProperties of tumorsPresentation machineryVascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumorNanomodulators targeting endothelial WNT and pericytes to reversibly open the blood–tumor barrier for boosted brain tumor therapy
Mu R, Sun H, Zeng Y, Tong Y, Tang P, Zhao M, Lv Z, Yu J, Chen Y, Lan Q, Zhen X, Han L. Nanomodulators targeting endothelial WNT and pericytes to reversibly open the blood–tumor barrier for boosted brain tumor therapy. Journal Of Controlled Release 2024, 369: 458-474. PMID: 38575077, DOI: 10.1016/j.jconrel.2024.03.047.Peer-Reviewed Original ResearchBreast cancer brain metastasesCancer brain metastasesBrain metastasesMedian survival of miceWnt signalingTumor-associated blood vesselsBlood-tumor barrierSurvival of miceBrain tumor therapyImproving chemotherapeutic efficiencyBrain-targeting drugsMedian survivalIntracranial edemaChemotherapeutic drugsICAM-1Tumor pericytesBrain entryTumor therapyChemotherapeutic efficiencyMetastasisInactivate Wnt signalingPericytesBlood vesselsIbrutinibBreast154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Robert S, Kiziltug E, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery. Neurosurgery 2024, 70: 35-36. DOI: 10.1227/neu.0000000000002809_154.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingInterferon-stimulated genesStereotactic radiosurgeryNatural killerMyeloid cellsImmune cellsRadiosurgical treatment of brain metastasesTreatment of brain metastasesCD4+ T cellsExpression of immune cellsMorbid side effectsTreatment of RNSubpopulations of myeloid cellsStereotactic radio surgeryMetastatic brain tumorsInvasive brain biopsyCellular immune profilesInflammatory immune responseCSF of patientsRN patientsBrain metastasesCD8+Immunotherapy optionsMetastatic tumors
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