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 radiosurgeryPre-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 studyCharacterizing Hearing Outcomes Following Treatment of Cerebellopontine Angle Meningiomas
Papazian M, Cottrell J, Pan L, Kay-Rivest E, Friedmann D, Jethanamest D, Kondziolka D, Pacione D, Sen C, Golfinos J, Roland J, McMenomey S. Characterizing Hearing Outcomes Following Treatment of Cerebellopontine Angle Meningiomas. Journal Of Neurological Surgery Part B Skull Base 2024 DOI: 10.1055/a-2399-0081.Peer-Reviewed Original ResearchInternal auditory canalCerebellopontine angle meningiomasRisk of hearing lossCerebellopontine angleStereotactic radiosurgeryHearing outcomesHearing lossSurgical patientsPredictors of hearing lossAssociated with hearing lossMultivariate Cox proportional hazards regression modelsPoor hearing outcomesSurgically treated lesionsHearing preservation ratePostoperative hearing lossPreservation of hearingTertiary care medical centerPreoperative imaging findingsCox proportional hazards regression modelsSurgically managed patientsCranial nerve VIIIAnalysis of patientsProportional hazards regression modelsHazards regression modelsParticipants Adult patientsNIRL-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 symptomsTyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC).
Miao E, Pike L, Boe L, Patil T, Myall N, Hui C, Pollom E, Qu V, Langston J, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Camidge D, Rusthoven C. Tyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 2019-2019. DOI: 10.1200/jco.2024.42.16_suppl.2019.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsUpfront stereotactic radiosurgeryCentral nervous systemTKI-naive patientsStereotactic radiosurgeryOverall survivalMultivariable adjustmentCNS controlNeurological symptomsCNS objective response rateOncogene-driven non-small cell lung cancerFirst-generation TKIsKinase inhibitorsUpfront tyrosine kinase inhibitorNon-small cell lung cancerCentral nervous system radiationGeneration tyrosine kinase inhibitorsEGFR-mutant NSCLCMulti-institutional seriesObjective response rateInferior overall survivalMedian follow-upTreatment of BMCell lung cancerCox proportional hazards models154 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 tumorsA large open access dataset of brain metastasis 3D segmentations on MRI with clinical and imaging information
Ramakrishnan D, Jekel L, Chadha S, Janas A, Moy H, Maleki N, Sala M, Kaur M, Petersen G, Merkaj S, von Reppert M, Baid U, Bakas S, Kirsch C, Davis M, Bousabarah K, Holler W, Lin M, Westerhoff M, Aneja S, Memon F, Aboian M. A large open access dataset of brain metastasis 3D segmentations on MRI with clinical and imaging information. Scientific Data 2024, 11: 254. PMID: 38424079, PMCID: PMC10904366, DOI: 10.1038/s41597-024-03021-9.Peer-Reviewed Original ResearchConceptsWhole-brain radiotherapyStereotactic radiosurgeryT1 post-contrastBrain metastasesPost-contrastSide effectsImage informationArtificial intelligenceAssociated with cognitive side effectsContrast-enhancing lesionsQuality of datasetsCognitive side effectsFLAIR MR imagesValidation of AI modelsBrain radiotherapyLimitations of algorithmsStandard treatmentAI modelsMR imagingAI networksContrast enhancementClinical settingSegmentation workflowDatasetClinical adoption
2023
SURG-32. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR BIOPSY-PROVEN RADIATION NECROSIS IN RADIOGRAPHICALLY RECURRENT BRAIN METASTASES
Strowd R, Chan M, Tatter S, Chiang V, Fecci P, Prabhu S, Hadjipanayis C, Kirkpatrick J, Sun D, Sinicrope K, Mohammadi A, Sevak P, Abram S, Kim A, Leuthardt E, Chao S, Phillips J, Lacroix M, Williams B, Placantonakis D, Silverman J, Baumgartner J, Piccioni D, Laxton A. SURG-32. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR BIOPSY-PROVEN RADIATION NECROSIS IN RADIOGRAPHICALLY RECURRENT BRAIN METASTASES. Neuro-Oncology 2023, 25: v269-v269. PMCID: PMC10640195, DOI: 10.1093/neuonc/noad179.1031.Peer-Reviewed Original ResearchLaser interstitial thermal therapyKarnofsky performance statusRadiation necrosisInterstitial thermal therapyBrain metastasesRadiographic progressionKaplan-MeierStereotactic radiosurgeryLocal controlMedian Karnofsky performance statusFuture radiographic progressionRadiotherapeutic treatment optionsResults Ninety patientsBrain metastasis patientsMulti-center registryRecurrent brain metastasesMedian hospitalization timeLesional progressionMultivariable FineNinety patientsSymptom controlCumulative incidenceMetastasis patientsPerformance statusSystemic therapySelected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study
Mange A, Singh C, Theriault B, Hansen J, An Y, Aneja S, Chiang V. Selected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study. International Journal Of Radiation Oncology • Biology • Physics 2023, 117: e135. DOI: 10.1016/j.ijrobp.2023.06.939.Peer-Reviewed Original ResearchMultiple brain metastasesBrain metastasesStereotactic radiosurgeryMedian KPSCommon indicationTumor characteristicsClinical trialsSRS treatmentSingle-institution retrospective studySubsequent-line treatmentMethods Clinical dataPatient selection criteriaTreatment of patientsSubset of lesionsNumber of lesionsDiagnosis of melanomaCNS progressionCNS radiationPrior WBRTOverall survivalPalliative treatmentPatient characteristicsProgressive diseaseImmunotherapy trialsSurvival groupSelected-Lesion Stereotactic Radiosurgery (SL-SRS) as a Novel Strategy in the Treatment of Patients With Multiple Brain Metastases
Theriault B, Singh C, Yu J, Knisely J, Shepard M, Wegner R, Warnick R, Peker S, Samanci Y, Trifiletti D, Lee C, Yang H, Bernstein K, Kondziolka D, Tripathi M, Mathieu D, Mantziaris G, Pikis S, Sheehan J, Chiang V. Selected-Lesion Stereotactic Radiosurgery (SL-SRS) as a Novel Strategy in the Treatment of Patients With Multiple Brain Metastases. Cureus 2023, 15: e45457. PMID: 37859877, PMCID: PMC10583225, DOI: 10.7759/cureus.45457.Peer-Reviewed Original ResearchWhole brain radiotherapyInternational Radiosurgery Research FoundationPrior whole brain radiotherapyBrain metastasesStereotactic radiosurgeryCommon reasonAsymptomatic brain metastasesNon-eloquent locationsSystemic treatment optionsMultiple brain metastasesPoor functional statusTreatment of patientsCentral nervous systemAttributable symptomsExtracranial diseaseSystemic therapyUntreated lesionsMedical oncologySystemic diseaseFunctional statusTreatment optionsClinical trialsSingle lesionLesion locationIntracranial lesionsCyberKnife Stereotactic Radiosurgery for Growing Vestibular Schwannoma: Longitudinal Tumor Control, Hearing Outcomes, and Predicting Post‐Treatment Hearing Status
Hildrew D, Perez P, Mady L, Li J, Nilsen M, Hirsch B. CyberKnife Stereotactic Radiosurgery for Growing Vestibular Schwannoma: Longitudinal Tumor Control, Hearing Outcomes, and Predicting Post‐Treatment Hearing Status. The Laryngoscope 2023, 134: s1-s12. PMID: 37178050, DOI: 10.1002/lary.30731.Peer-Reviewed Original ResearchConceptsTumor control rateCyberKnife stereotactic radiosurgeryHearing outcomesVestibular schwannomaControl rateStereotactic radiosurgeryRetrospective case series reviewCase series reviewThird of patientsProportional hazard modelingMaximum radiation doseSeries reviewTumor controlAvailable audiogramsOtolaryngology-HeadTumor volumeEffective treatmentClass APatientsHearing statusAmerican AcademyHazard modelingVolumetric analysisRadiation doseOutcomesUse of stereotactic radiosurgery in treatment of brain metastases from pediatric extracranial solid tumors
Xu S, Campbell A, Chiang V, Bindra R, Vasquez J, Pashankar F. Use of stereotactic radiosurgery in treatment of brain metastases from pediatric extracranial solid tumors. Pediatric Blood & Cancer 2023, 70: e30303. PMID: 36975152, DOI: 10.1002/pbc.30303.Peer-Reviewed Original ResearchLocal Control and Survival Outcomes After Stereotactic Radiosurgery for Brain Metastases From Gastrointestinal Primaries: An International Multicenter Analysis
Singh R, Bowden G, Mathieu D, Perlow H, Palmer J, Elhamdani S, Shepard M, Liang Y, Nabeel A, Reda W, Tawadros S, Abdelkarim K, El-Shehaby A, Emad R, Elazzazi A, Warnick R, Gozal Y, Daly M, McShane B, Addis-Jackson M, Karthikeyan G, Smith S, Picozzi P, Franzini A, Kaisman-Elbaz T, Yang H, Wei Z, Legarreta A, Hess J, Templeton K, Pikis S, Mantziaris G, Simonova G, Liscak R, Peker S, Samanci Y, Chiang V, Niranjan A, Kersh C, Lee C, Trifiletti D, Lunsford L, Sheehan J. Local Control and Survival Outcomes After Stereotactic Radiosurgery for Brain Metastases From Gastrointestinal Primaries: An International Multicenter Analysis. Neurosurgery 2023, 93: 592-598. PMID: 36942965, DOI: 10.1227/neu.0000000000002456.Peer-Reviewed Original ResearchConceptsKarnofsky performance statusStereotactic radiosurgeryOverall survivalBrain metastasesUnivariate analysisLocal controlGI primaryExtracranial metastasesPrognostic factorsBrain metastases treated with stereotactic radiosurgeryAssociated with inferior LCAssociated with inferior OSMedian Karnofsky performance statusEvaluate potential prognostic factorsInternational multicenter analysisPlanning target volumePotential prognostic factorsKaplan-Meier analysisOne-yearProportional hazards modelInferior LCInferior OSOS ratesLC ratesGastrointestinal primaryOutcomes of patients with brain metastases from renal cell carcinoma treated with first-line therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Takemura K, Lemelin A, Ernst M, Wells C, Basappa N, Szabados B, Powles T, Davis I, Wood L, Kapoor A, McKay R, Lee J, Meza L, Pal S, Donskov F, Yuasa T, Beuselinck B, Gebrael G, Choueiri T, Heng D. Outcomes of patients with brain metastases from renal cell carcinoma treated with first-line therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Journal Of Clinical Oncology 2023, 41: 600-600. DOI: 10.1200/jco.2023.41.6_suppl.600.Peer-Reviewed Original ResearchInternational Metastatic Renal Cell Carcinoma Database ConsortiumFirst-line therapyRenal cell carcinomaAssociated with longer OSAnti-VEGF monotherapyAnti-VEGFBrain metastasesOutcomes of patientsBaseline patient characteristicsStable diseaseComplete responsePartial responseOverall survivalCombination therapyStereotactic radiosurgeryLonger OSLocal therapyPatient characteristicsInitiation of first-line therapyBest overall responseWhole-brain radiotherapyCohort of patientsProportion of patientsCell carcinomaDisease sitesManagement of patients with brain metastases from NSCLC without a genetic driver alteration: upfront radiotherapy or immunotherapy?
Merkin R, Chiang V, Goldberg S. Management of patients with brain metastases from NSCLC without a genetic driver alteration: upfront radiotherapy or immunotherapy? Therapeutic Advances In Medical Oncology 2023, 15: 17588359231175438. PMID: 37275964, PMCID: PMC10233588, DOI: 10.1177/17588359231175438.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsBrain metastasesTargetable genetic alterationsLocal therapyLung cancerStereotactic radiosurgeryDeath 1 ligand 1 expressionManagement of BMSole metastatic siteStage IV diseaseWhole brain radiotherapyLigand 1 expressionPD-L1 expressionProspective clinical trialsTime of diagnosisManagement of patientsCell lung cancerCancer-related deathGenetic alterationsCentral nervous systemGenetic driver alterationsAnaplastic lymphoma kinaseEpidermal growth factor receptorGrowth factor receptorUpfront radiotherapy
2022
Multicenter analysis of stereotactic radiosurgery for multiple brain metastases from EGFR and ALK driven non-small cell lung cancer
Wandrey N, Gao D, Robin T, Contessa J, Singh C, Chiang V, Li J, Chen A, Wang Y, Sheehan J, Dutta S, Weiss S, Paly J, Rusthoven C. Multicenter analysis of stereotactic radiosurgery for multiple brain metastases from EGFR and ALK driven non-small cell lung cancer. Lung Cancer 2022, 176: 144-148. PMID: 36641932, PMCID: PMC10552603, DOI: 10.1016/j.lungcan.2022.11.019.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerOverall survivalCell lung cancerStereotactic radiosurgeryBrain metastasesMultivariable adjustmentMulticenter analysisLung cancerNext-generation tyrosine kinase inhibitorsSRS treatmentOnly negative prognostic factorWhole brain radiotherapyMedian overall survivalMultiple brain metastasesNegative prognostic factorFavorable overall survivalTyrosine kinase inhibitorsTreatment 1CNS progressionMulticenter outcomesMedian followPrognostic factorsFavorable prognosisCNS diseaseTreatment optionsAssociation of circulating markers with cognitive decline after radiation therapy for brain metastasis.
Huntoon K, Anderson S, Ballman K, Twohy E, Dooley K, Jiang W, An Y, Li J, von Roemeling C, Qie Y, Ross O, Cerhan J, Whitton A, Greenspoon J, Parney I, Ashman J, Bahary J, Hadjipanayis C, Urbanic J, Farace E, Khuntia D, Laack N, Brown P, Roberge D, Kim B. Association of circulating markers with cognitive decline after radiation therapy for brain metastasis. Neuro-Oncology 2022, 25: 1123-1131. PMID: 36472389, PMCID: PMC10237411, DOI: 10.1093/neuonc/noac262.Peer-Reviewed Original ResearchConceptsWhole-brain radiation therapyStereotactic radiosurgeryBrain metastasesRadiation therapyNeurocognitive declineSerum levelsRadiation-induced neurocognitive declinePretreatment serum markersLow serum levelsAssociated with neurocognitive impairmentRandomized clinical trialsEnzyme-linked immunosorbent assaySurgical resectionSecondary endpointsSerum markersRetrospective analysisClinical trialsNeurocognitive impairmentCognitive impairmentMetastasisBlood samplesImmunosorbent assayMonthsSecondary analysisTherapyStereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer.
Kowalchuk R, Niranjan A, Hess J, Antonios J, Zhang M, Braunstein S, Ross R, Pikis S, Deibert C, Lee C, Yang H, Langlois A, Mathieu D, Peker S, Samanci Y, Rusthoven C, Chiang V, Wei Z, Lunsford L, Trifiletti D, Sheehan J. Stereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer. Journal Of Neurosurgery 2022, 138: 1608-1614. PMID: 36433878, DOI: 10.3171/2022.10.jns221900.Peer-Reviewed Original ResearchTriple-negative breast cancerLocal tumor progressionStereotactic radiosurgeryBreast cancerOverall survivalMetastatic lesionsPerformance statusLocal controlTriple-negative breast cancer metastasisMedian Karnofsky performance statusTumor progressionWhole-brain radiation therapyFavorable performance statusMedian margin dosePrior stereotactic radiosurgerySymptomatic radiation necrosisKarnofsky performance statusIntracranial metastatic diseaseRetrospective chart reviewLocal tumor controlBreast cancer metastasisIntracranial metastatic lesionsMargin doseMultiinstitutional cohortBrain metastases
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