2024
A 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 rateNeratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆
Freedman R, Heiling H, Li T, Trapani D, Tayob N, Smith K, Davis R, Pereslete A, DeMeo M, Cotter C, Chen W, Parsons H, Santa-Maria C, Van Poznak C, Moy B, Brufsky A, Melisko M, O’Sullivan C, Ashai N, Rauf Y, Nangia J, Burns R, Savoie J, Wolff A, Winer E, Rimawi M, Krop I, Lin N. Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆. Annals Of Oncology 2024, 35: 993-1002. PMID: 38977064, DOI: 10.1016/j.annonc.2024.07.245.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesT-DM1Ado-trastuzumab emtansineCentral nervous systemOverall survivalCNS objective response rateEfficacy of neratinibT-DM1 exposureObjective response rateCancer brain metastasesPhase II studyMedian OSRANO-BMBrain MetastasesSlow accrualIntracranial activityII studyPrimary endpointPreclinical dataCohort 4Response assessmentTreatment optionsNeratinibPatientsHLA 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 machineryNanomodulators 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 vesselsIbrutinibBreast
2023
PACS-Integrated Tools for Peritumoral Edema Volumetrics Provide Additional Information to RANO-BM-Based Assessment of Lung Cancer Brain Metastases after Stereotactic Radiotherapy: A Pilot Study
Kaur M, Petersen G, Jekel L, von Reppert M, Varghese S, de Oliveira Santo I, Avesta A, Aneja S, Omuro A, Chiang V, Aboian M. PACS-Integrated Tools for Peritumoral Edema Volumetrics Provide Additional Information to RANO-BM-Based Assessment of Lung Cancer Brain Metastases after Stereotactic Radiotherapy: A Pilot Study. Cancers 2023, 15: 4822. PMID: 37835516, PMCID: PMC10571649, DOI: 10.3390/cancers15194822.Peer-Reviewed Original ResearchPost-SRTStereotactic radiotherapyLung cancer brain metastasesCancer brain metastasesPost-contrast T1-weighted imagesSignificant clinical symptomsContrast-enhancing tumorT1-weighted imagesCritical additional informationEdema changesBrain metastasesClinical symptomsCare treatmentHyperintense volumeEdema assessmentLesion changesLesion sizeEdemaDifferent timepointsPilot studyRadiotherapyLesionsVolumetric changesAdditional informationMETSBSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structuresBSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES
Vilarino N, de Rodas M, Lu B, Goldberg S, Schalper K. BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402438, DOI: 10.1093/noajnl/vdad070.012.Peer-Reviewed Original ResearchLung cancer brain metastasesPrimary lung tumorsImmune checkpoint inhibitorsCancer brain metastasesBrain metastasesPresentation machineryClinicopathologic variablesHLA classTumor cell PD-L1 expressionBackground Immune checkpoint inhibitorsLocal adaptive immune responseHLA Class I AntigenPD-L1 expressionDuration of responseB2MAdaptive immune responsesDistinct immunomodulatory propertiesImmune evasion mechanismsClass I AntigenIFN-γ signalingIRF-1Interferon regulatory factor 1Checkpoint inhibitorsMost patientsWorse survivalPeritumoral edema measurements provide additional information to RANO-BM based assessment of lung cancer brain metastases after Gamma Knife therapy (P10-13.002)
Kaur M, Cassinelli G, von Reppert M, Jekel L, Varghese S, Dixe I, Omuro A, Chiang V, Aboian M. Peritumoral edema measurements provide additional information to RANO-BM based assessment of lung cancer brain metastases after Gamma Knife therapy (P10-13.002). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000203091.Peer-Reviewed Original Research
2022
Clinical outcomes of non-small cell lung cancer brain metastases treated with stereotactic radiosurgery and immune checkpoint inhibitors, EGFR tyrosine kinase inhibitors, chemotherapy and immune checkpoint inhibitors, or chemotherapy alone.
Dohm A, Tang J, Mills M, Liveringhouse C, Sandoval M, Perez B, Robinson T, Creelan B, Gray J, Etame A, Vogelbaum M, Forsyth P, Yu H, Oliver D, Ahmed K. Clinical outcomes of non-small cell lung cancer brain metastases treated with stereotactic radiosurgery and immune checkpoint inhibitors, EGFR tyrosine kinase inhibitors, chemotherapy and immune checkpoint inhibitors, or chemotherapy alone. Journal Of Neurosurgery 2022, 138: 1600-1607. PMID: 36681988, DOI: 10.3171/2022.9.jns221896.Peer-Reviewed Original ResearchEpidermal growth factor receptor tyrosine kinase inhibitorsImmune checkpoint inhibitorsDistant intracranial controlNon-small cell lung cancer brain metastasesCell lung cancer brain metastasesLung cancer brain metastasesCancer brain metastasesSystemic therapyBrain metastasesStereotactic radiosurgeryCheckpoint inhibitorsLocal controlGrowth factor receptor tyrosine kinase inhibitorsSingle-fraction stereotactic radiosurgeryReceptor tyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsKinase inhibitorsChemotherapy-alone groupNSCLC BM patientsNSCLC brain metastasesTyrosine kinase inhibitorsBM diagnosisIntracranial controlBM patientsOverall survivalPreclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clinical Cancer Research 2022, 29: 174-182. PMID: 36074155, PMCID: PMC9811155, DOI: 10.1158/1078-0432.ccr-22-1138.Peer-Reviewed Original ResearchConceptsBreast cancer brain metastasesActive brain metastasesObjective response rateCNS objective response rateCancer brain metastasesBrain metastasesT-DXdPatient-derived xenograftsPDX modelsCohort studyTrastuzumab deruxtecanClinical efficacyClinical trialsHER2-positive breast cancer brain metastasesMetastatic HER2-positive breast cancerResponse rateMulti-institutional cohort studyHER2-positive breast cancerRetrospective multi-institutional cohort studyOrthotopic patient-derived xenograftsRetrospective cohort studyProspective clinical trialsSubset of patientsCentral nervous system activityPivotal clinical trialsp16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Ni J, Kabraji S, Xie S, Wang Y, Pan P, He X, Liu Z, Leone JP, Long HW, Brown MA, Winer EP, Dillon DAR, Lin NU, Zhao JJ. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications 2022, 13: 1473. PMID: 35304445, PMCID: PMC8933392, DOI: 10.1038/s41467-022-29081-2.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsBrain metastasesMetastatic HER2-positive breast cancerBiomarker-driven clinical trialsBreast cancer brain metastasesHER2-positive breast cancerOrthotopic patient-derived xenograftsMajority of HER2Cancer brain metastasesCDK4/6 inhibitionProtein immunohistochemistryClinical trialsBreast cancerHER2Tumor suppressor p16INK4aPatientsMetastasisBCBMAbemaciclibTucatinibXenograftsImmunohistochemistryCancerCDK4/6Trials
2021
Clinical Outcomes of Non-Small Cell Lung Cancer Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Inhibitors, EGFR Tyrosine Kinase Inhibitors, Chemotherapy and Immune Checkpoint Inhibitors, or Chemotherapy Alone
Dohm A, Tang J, Mills M, Perez B, Robinson T, Creelan B, Gray J, Etame A, Vogelbaum M, Forsyth P, Yu H, Oliver D, Ahmed K. Clinical Outcomes of Non-Small Cell Lung Cancer Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Inhibitors, EGFR Tyrosine Kinase Inhibitors, Chemotherapy and Immune Checkpoint Inhibitors, or Chemotherapy Alone. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: e567. DOI: 10.1016/j.ijrobp.2021.07.1531.Peer-Reviewed Original ResearchEpidermal growth factor receptor tyrosine kinase inhibitorsImmune checkpoint inhibitorsDistant intracranial controlNon-small cell lung cancer brain metastasesCell lung cancer brain metastasesLung cancer brain metastasesTiming of SRSChemotherapy-alone groupNSCLC BM patientsNSCLC brain metastasesBrain metastasesCancer brain metastasesSystemic therapyRadiation necrosisStereotactic radiosurgeryCheckpoint inhibitorsOverall survivalTreatment groupsLocal controlMultivariate analysisBM patientsAlone groupClinical outcomesConventional chemotherapyGrowth factor receptor tyrosine kinase inhibitorsSYST-06. PHASE II TRIAL OF PAXALISIB (GDC-0084) IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM)
Leone J, Tayob N, Pereslete A, Ligibel J, Parsons H, Bi W, Zhao J, Winer E, Lin N. SYST-06. PHASE II TRIAL OF PAXALISIB (GDC-0084) IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM). Neuro-Oncology Advances 2021, 3: iv9-iv9. DOI: 10.1093/noajnl/vdab112.034.Peer-Reviewed Original ResearchBreast cancer brain metastasesObjective response rateCohort BCohort ACNS metastasesPrimary endpointHER2-positive breast cancer brain metastasesNeuro-Oncology Brain Metastases criteriaCentral nervous system metastasesHER2-positive breast cancerPatient-derived xenografts (PDX) modelsPhase II cohortNervous system metastasesPhase II studyCancer brain metastasesPhase II trialPI3K/Akt/mTORPatient-reported outcomesPI3KBrain-penetrant inhibitorAkt/mTORMetastasis (TNM) criteriaBrain metastasesII trialMetastasis resectionOTHR-11. Comprehensive Analysis of Driver Mutation Profile in a Cohort of Lung Cancer Patients Using Targeted Gene Panel Analysis with Focus on Brain Metastatic Disease
Kazarian M, Cui J, Tocino I, Mahajan A, Aboian M. OTHR-11. Comprehensive Analysis of Driver Mutation Profile in a Cohort of Lung Cancer Patients Using Targeted Gene Panel Analysis with Focus on Brain Metastatic Disease. Neuro-Oncology Advances 2021, 3: iii16-iii16. PMCID: PMC8351181, DOI: 10.1093/noajnl/vdab071.066.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesDeep white matterLung cancerGene panel analysisWhite matterLung cancer brain metastasesHospital tumor registryTertiary referral institutionCancer brain metastasesProportion of patientsBrain metastatic diseaseMajority of patientsBrain metastatic lesionsCell lung cancerLung cancer patientsLung cancer cohortTargeted Gene Panel AnalysisLung cancer diagnosisMolecular signaturesNext-generation sequencing resultsMetastatic diseasePatient demographicsTumor RegistryMetastatic lesionsENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody
Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray N, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6: e145875. PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.Peer-Reviewed Original ResearchConceptsBlood-brain barrierAnti-DNA autoantibodiesBrain tumorsBreast cancer brain metastasesBlood-brain barrier transportBrain tumor immunotherapyCancer brain metastasesBrain endothelial cellsEndothelial cell penetrationCNS lupusNeurotoxic autoantibodiesBrain metastasesTumor immunotherapyBarrier transportAntibody-based approachesCNS penetrationAutoantibodiesEfficacy studiesOrthotopic glioblastomaEndothelial cellsTumorsCancer cellsNucleoside fluxesActionable mechanismsKey transportersNivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: A non-randomized, open-label phase Ib study.
Ahmed K, Kim Y, Arrington J, Kim S, DeJesus M, Soyano A, Armaghani A, Costa R, Khong H, Rosa M, Caudell J, Diaz R, Robinson T, Etame A, Tran N, Sahebjam S, Soliman H, Forsyth P, Yu H, Han H. Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: A non-randomized, open-label phase Ib study. Journal Of Clinical Oncology 2021, 39: e14010-e14010. DOI: 10.1200/jco.2021.39.15_suppl.e14010.Peer-Reviewed Original ResearchBreast cancer brain metastasesCancer brain metastasesProgression-free survivalBrain metastasesStereotactic radiosurgeryBrain metastasis controlStudy therapyControl rateMetastasis controlCertain breast cancer patientsNeuro-Oncology Brain MetastasesSystemic progression-free survivalDose of nivolumabNeurologic adverse eventsImmune checkpoint inhibitionPhase Ib studyPhase Ib trialSolid Tumors criteriaResponse Evaluation CriteriaKey eligibility criteriaTumor control rateFeasible treatment optionBreast cancer patientsBrain metastasis managementExtracranial diseaseAbstract PO-041: An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases
Jansen C, del Balzo L, Prabhu R, Logan S, Chappa P, Patel K, Wilkinson S, Lake R, Shu H, Zhong J, Dhere V, Olson J, Sowalsky A, Khan M, Kissick H, Buchwald Z. Abstract PO-041: An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases. Clinical Cancer Research 2021, 27: po-041-po-041. DOI: 10.1158/1557-3265.radsci21-po-041.Peer-Reviewed Original ResearchCD8+ T cellsStem-like CD8+ T cellsNon-small cell lung cancer brain metastasisNon-small cell lung cancerAntigen presenting cellsLung cancer brain metastasisStereotactic radiosurgeryBrain metastasesCancer brain metastasesImmune nicheT cellsPresenting cellsMHC-II+TCF-1CD8+ T cell infiltrationImmunological nichePost-operative stereotactic radiosurgeryPre-operative stereotactic radiosurgeryT cell infiltrationCell lung cancerCohort of patientsCheckpoint blockadePD-1Disease recurrenceGenitourinary malignancies
2020
Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases
Leone JP, Emblem KE, Weitz M, Gelman RS, Schneider BP, Freedman RA, Younger J, Pinho MC, Sorensen AG, Gerstner ER, Harris G, Krop IE, Morganstern D, Sohl J, Hu J, Kasparian E, Winer EP, Lin NU. Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases. Breast Cancer Research 2020, 22: 131. PMID: 33256829, PMCID: PMC7706261, DOI: 10.1186/s13058-020-01372-w.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBrainBrain NeoplasmsBreastBreast NeoplasmsCarboplatinFemaleGenotyping TechniquesHumansKaplan-Meier EstimateMagnetic Resonance ImagingMiddle AgedPolymorphism, Single NucleotideProgression-Free SurvivalTrastuzumabVascular Endothelial Growth Factor AConceptsProgression-free survivalBreast cancer brain metastasesEarly MRI changesCancer brain metastasesBrain metastasesOverall survivalMRI changesBreast cancerEastern Cooperative Oncology Group performance statusDay 1Cycle 1 day 1Cycle 1 day 8Median progression-free survivalWorse progression-free survivalRegimen warrants further investigationDurable objective responsesECOG PS 1Efficacy of bevacizumabHER2-positive diseaseProgressive brain metastasesResultsThirty-eight patientsMedian overall survivalObjective response ratePhase II trialContrast-enhanced brain MRIRADT-02. CLINICAL OUTCOMES OF BREAST BRAIN METASTASES BY SUBTYPE FOLLOWING LINAC BASED STEREOTACTIC RADIATION
Thawani C, Mills M, Figura N, Sarangkasiri S, Washington I, Robinson T, Diaz R, Etame A, Vogelbaum M, Yu H, Ahmed K. RADT-02. CLINICAL OUTCOMES OF BREAST BRAIN METASTASES BY SUBTYPE FOLLOWING LINAC BASED STEREOTACTIC RADIATION. Neuro-Oncology 2020, 22: ii181-ii182. PMCID: PMC7651564, DOI: 10.1093/neuonc/noaa215.757.Peer-Reviewed Original ResearchBreast cancer subtypesBreast cancer brain metastasesBrain metastasis diagnosisCancer brain metastasesBrain metastasesStereotactic radiationOverall survivalClinical outcomesCancer subtypesHR-/HER2TN patientsMetastasis diagnosisHormone receptorsBreast cancer patientsBrain metastasis controlBreast brain metastasesOS ratesClinical chartsInstitutional seriesMedian ageSystemic metastasesInstitutional registryCancer patientsRadiologic examinationDisease progressionClinical Outcomes of Breast Cancer Brain Metastases Treated with Stereotactic Radiation and Capecitabine
Mills M, Naz A, Thawani C, Walker C, Figura N, Forsyth P, Etame A, Liu J, Vogelbaum M, Yu M, Robinson T, Soliman H, Han H, Ahmed K. Clinical Outcomes of Breast Cancer Brain Metastases Treated with Stereotactic Radiation and Capecitabine. International Journal Of Radiation Oncology • Biology • Physics 2020, 108: e685-e686. DOI: 10.1016/j.ijrobp.2020.07.2040.Peer-Reviewed Original Research
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