2024
Patterns 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, 1-7. 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 studyExecutive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer
Nagpal S, Milano M, Chiang V, Soltys S, Brackett A, Halasz L, Garg A, Sahgal A, Ahluwalia M, Tom M, Palmer J, Knisley J, Chao S, Gephart M, Wang T, Lo S, Chang E. Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer. Neuro-Oncology 2024, 26: 1195-1212. PMID: 38459978, PMCID: PMC11226873, DOI: 10.1093/neuonc/noae041.Peer-Reviewed Original ResearchNon-small cell lung cancerTyrosine kinase inhibitorsCell lung cancerCentral nervous systemAmerican Radium SocietyALK-fusionBrain metastasesAmerican Radium Society Appropriate Use CriteriaLung cancerSequence of tyrosine kinase inhibitorsALK tyrosine kinase inhibitorsTreatment of brain metastasesEGFR tyrosine kinase inhibitorsWhole-brain RTEpidermal growth factor receptorGrowth factor receptorAppropriate Use CriteriaBrain RTEGFR-mutantRadiotherapyTreatment optionsFactor receptorKinase inhibitorsNervous systemLiterature search
2023
Management 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 optionsBrain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentGraded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors
Sperduto PW, De B, Li J, Carpenter D, Kirkpatrick J, Milligan M, Shih HA, Kutuk T, Kotecha R, Higaki H, Otsuka M, Aoyama H, Bourgoin M, Roberge D, Dajani S, Sachdev S, Gainey J, Buatti JM, Breen W, Brown PD, Ni L, Braunstein S, Gallitto M, Wang TJC, Shanley R, Lou E, Shiao J, Gaspar LE, Tanabe S, Nakano T, An Y, Chiang V, Zeng L, Soliman H, Elhalawani H, Cagney D, Thomas E, Boggs DH, Ahluwalia MS, Mehta MP. Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors. International Journal Of Radiation Oncology • Biology • Physics 2022, 114: 60-74. PMID: 35331827, PMCID: PMC9378572, DOI: 10.1016/j.ijrobp.2022.03.020.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSmall cell lung cancerGraded Prognostic AssessmentBrain metastasesSignificant prognostic factorsPrognostic factorsDeath ligand 1Cell lung cancerLung cancerPD-L1Lung adenocarcinomaMedian survivalNSCLC adenocarcinomaPrognostic assessmentInitial reportMulti-institutional retrospective databaseProgrammed Death Ligand 1PD-L1 1Tumor molecular statusOverall median survivalPD-L1 expressionLigand 1Anaplastic lymphoma kinaseEpidermal growth factor receptorGrowth factor receptor
2021
Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF)
Cifarelli C, Vargo J, Fang W, Liscak R, Guseynova K, Warnick R, Lee C, Yang H, Borghei-Razavi H, Maiti T, Siddiqui Z, Yuan J, Grills I, Mathieu D, Touchette C, Cordeiro D, Chiang V, Hess J, Tien C, Faramand A, Kano H, Barnett G, Sheehan J, Lunsford L. Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF). Neurosurgery 2021, 89: s20-s20. DOI: 10.1093/neuros/nyz428_s020.Peer-Reviewed Original ResearchReirradiation With Stereotactic Radiosurgery After Local or Marginal Recurrence of Brain Metastases From Previous Radiosurgery
Kowalchuk RO, Niranjan A, Lee CC, Yang HC, Liscak R, Guseynova K, Tripathi M, Kumar N, Peker S, Samanci Y, Hess J, Chiang V, Iorio-Morin C, Mathieu D, Pikis S, Wei Z, Lunsford LD, Trifiletti DM, Sheehan JP. Reirradiation With Stereotactic Radiosurgery After Local or Marginal Recurrence of Brain Metastases From Previous Radiosurgery. International Journal Of Radiation Oncology • Biology • Physics 2021, 112: 726-734. PMID: 34644606, DOI: 10.1016/j.ijrobp.2021.10.008.Peer-Reviewed Original ResearchConceptsLocal tumor controlRepeat stereotactic radiosurgeryRadiation necrosisStereotactic radiosurgeryBrain metastasesTumor controlMaximum doseMarginal recurrenceBiopsy-proven non-small cell lung cancerIsodose lineNon-small cell lung cancerRisk of RNPreoperative stereotactic radiosurgeryPrior stereotactic radiosurgerySymptomatic radiation necrosisNeuro-Oncology criteriaCell lung cancerPrescription isodose linePrevious radiosurgeryMargin dosePrimary endpointPrior immunotherapyLung cancerMajor indicationTumor volume
2020
Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases
Rusthoven CG, Yamamoto M, Bernhardt D, Smith DE, Gao D, Serizawa T, Yomo S, Aiyama H, Higuchi Y, Shuto T, Akabane A, Sato Y, Niranjan A, Faramand AM, Lunsford LD, McInerney J, Tuanquin LC, Zacharia BE, Chiang V, Singh C, Yu JB, Braunstein S, Mathieu D, Touchette CJ, Lee CC, Yang HC, Aizer AA, Cagney DN, Chan MD, Kondziolka D, Bernstein K, Silverman JS, Grills IS, Siddiqui ZA, Yuan JC, Sheehan JP, Cordeiro D, Nosaki K, Seto T, Deibert CP, Verma V, Day S, Halasz LM, Warnick RE, Trifiletti DM, Palmer JD, Attia A, Li B, Cifarelli CP, Brown PD, Vargo JA, Combs SE, Kessel KA, Rieken S, Patel S, Guckenberger M, Andratschke N, Kavanagh BD, Robin TP. Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases. JAMA Oncology 2020, 6: 1028-1037. PMID: 32496550, PMCID: PMC7273318, DOI: 10.1001/jamaoncol.2020.1271.Peer-Reviewed Original ResearchConceptsWhole brain radiotherapyProgression-free survivalSmall-cell lung cancer (SCLC) brain metastasesCell lung cancer brain metastasesCNS progression-free survivalLung cancer brain metastasesPropensity score-matched analysisMedian overall survivalCancer brain metastasesBrain metastasesOverall survivalStereotactic radiosurgeryCentral nervous system (CNS) progression-free survivalMedian CNS progression-free survivalSRS outcomesCentral nervous system progressionSmall cell lung cancerLimited brain metastasesMulticenter cohort studyDisease control statusCell lung cancerSingle-arm trialStandard of careLeptomeningeal progressionWBRT cohortMulti-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy.
Miccio JA, Barsky A, Gao S, Verma V, Noticewala SS, Jairam V, Johnson SB, Yu JB, Hansen JE, Aneja S, An Y, Decker RH, Bulent Omay S, Li J, Kurtz GA, Alonso-Basanta M, Lee JYK, Chiang VL, Park HS. Multi-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy. Journal Of Radiosurgery And SBRT 2020, 7: 19-27. PMID: 32802575, PMCID: PMC7406345.Peer-Reviewed Original ResearchWhole brain radiotherapyBrain metastasesOverall survivalNeurologic deathSmall-cell lung cancer (SCLC) brain metastasesCell lung cancer brain metastasesLung cancer brain metastasesSalvage whole brain radiotherapyMulti-institutional retrospective reviewSmall cell lung cancerMost SCLC patientsSCLC brain metastasesTime of SRSMedian overall survivalCancer brain metastasesCell lung cancerIntracranial progressionSCLC patientsUpfront radiosurgeryBrain radiationBrain radiotherapySelect patientsRetrospective reviewLung cancerStereotactic radiosurgery
2019
Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF)
Cifarelli CP, Vargo JA, Fang W, Liscak R, Guseynova K, Warnick RE, Lee CC, Yang HC, Borghei-Razavi H, Maiti T, Siddiqui ZA, Yuan JC, Grills IS, Mathieu D, Touchette CJ, Cordeiro D, Chiang V, Hess J, Tien CJ, Faramand A, Kano H, Barnett GH, Sheehan JP, Lunsford LD. Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF). Neurosurgery 2019, 87: 664-671. PMID: 31599324, PMCID: PMC7780439, DOI: 10.1093/neuros/nyz428.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerWhole-brain irradiationSCLC brain metastasesInternational Radiosurgery Research FoundationDistant brain failureBrain metastasesOverall survivalStereotactic radiosurgerySCLC patientsBrain failureLung cancerPrior whole-brain irradiationMulti-institutional retrospective reviewKaplan-Meier survival analysisCox proportional hazards modelLocal failureProphylactic cranial irradiationInstitutional retrospective studyMedian marginal doseOngoing prospective trialsCell lung cancerGamma knife radiosurgeryInstitutional review boardValue of radiosurgeryBinary logistic regressionLocal 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
Durability of brain metastasis response and overall survival in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab.
Goldberg S, Gettinger S, Mahajan A, Herbst R, Chiang A, Lilenbaum R, Jilaveanu L, Rowen E, Gerrish H, Komlo A, Wei W, Chiang V, Kluger H. Durability of brain metastasis response and overall survival in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab. Journal Of Clinical Oncology 2018, 36: 2009-2009. DOI: 10.1200/jco.2018.36.15_suppl.2009.Peer-Reviewed Original Research
2017
Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in the United States.
Kann BH, Park HS, Johnson SB, Chiang VL, Yu JB. Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in the United States. Journal Of The National Comprehensive Cancer Network 2017, 15: 1494-1502. PMID: 29223987, DOI: 10.6004/jnccn.2017.7003.Peer-Reviewed Original ResearchConceptsNational Cancer Data BaseStereotactic radiosurgeryBrain metastasesPractice patternsBrain radiotherapyMetastatic diseaseMetastatic non-small cell lung cancerNon-small cell lung cancerNon-SR patientsUpfront brain radiotherapyNational practice patternsProportion of patientsKaplan-Meier methodCell lung cancerProportion of facilitiesQuality of lifeChi-square testActuarial survivalIntracranial controlNeurocognitive toxicityNonprivate insuranceSRS useNCDB analysisDiagnosis yearMultivariable analysisEstimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)
Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, Shanley R, Yeh N, Gaspar LE, Braunstein S, Sneed P, Boyle J, Kirkpatrick JP, Mak KS, Shih HA, Engelman A, Roberge D, Arvold ND, Alexander B, Awad MM, Contessa J, Chiang V, Hardie J, Ma D, Lou E, Sperduto W, Mehta MP. Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA). JAMA Oncology 2017, 3: 827-831. PMID: 27892978, PMCID: PMC5824323, DOI: 10.1001/jamaoncol.2016.3834.Peer-Reviewed Original ResearchConceptsDiagnosis-Specific Graded Prognostic AssessmentBrain metastasesGraded Prognostic AssessmentFuture clinical trialsLung cancerLung-molGPAMedian survivalPrognostic factorsHazard ratioClinical trialsMAIN OUTCOMEPrognostic assessmentLung-molGPA scoreOverall median survivalKarnofsky performance statusMultiple Cox regressionSignificant prognostic factorsCell lung cancerRetrospective database analysisCancer-related mortalityLog-rank testHeterogeneous patient populationClinical decision makingExtracranial metastasesOverall survivalManagement of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis
Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. Journal Of Clinical Oncology 2017, 35: jco.2016.69.714. PMID: 28113019, DOI: 10.1200/jco.2016.69.7144.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungCombined Modality TherapyCranial IrradiationDisease-Free SurvivalErbB ReceptorsErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsRadiosurgeryRetrospective StudiesSalvage TherapySurvival RateConceptsWhole brain radiotherapyMulti-institutional analysisEGFR-mutant NSCLCBrain metastasesEGFR-TKIStereotactic radiosurgeryTyrosine kinase inhibitorsOverall survivalEpidermal growth factor receptorGrowth factor receptorIntracranial progressionLung cancerMutant non-small cell lung cancerEGFR-TKI resistance mutationNon-small cell lung cancerIntracranial progression-free survivalRetrospective multi-institutional analysisDeferral of radiotherapyEGFR-TKI useSimilar prognostic featuresUpfront EGFR-TKIProgression-free survivalFactor receptorInferior overall survivalCell lung cancer
2016
Deferring Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Non-Small Cell Lung Cancer: A Multi-Institutional Analysis
Magnuson W, Amini A, Patil T, Kavanagh B, Camidge D, Braunstein S, Boreta L, Attia A, Rana N, Contessa J, Gettinger S, Lester-Coll N, Yu J, Chiang V. Deferring Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Non-Small Cell Lung Cancer: A Multi-Institutional Analysis. International Journal Of Radiation Oncology • Biology • Physics 2016, 96: s57-s58. DOI: 10.1016/j.ijrobp.2016.06.149.Peer-Reviewed Original ResearchPembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohortImpact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases
Magnuson WJ, Yeung JT, Guillod PD, Gettinger SN, Yu JB, Chiang VL. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2016, 95: 673-679. PMID: 27034176, DOI: 10.1016/j.ijrobp.2016.01.037.Peer-Reviewed Original ResearchConceptsWhole-brain radiation therapyUpfront EGFR-TKIIntracranial progression-free survivalUpfront radiation therapyProgression-free survivalBrain metastasesEGFR-TKI groupEGFR-TKIEGFR-mutant NSCLCOverall survivalRadiation therapyEpidermal Growth Factor Receptor–Mutant NonDisease-specific Graded Prognostic AssessmentUpfront EGFR tyrosine kinase inhibitorsEGFR-TKI resistance mutationSmall cell lung cancerEGFR tyrosine kinase inhibitorsEGFR-TKI useMedian overall survivalSimilar overall survivalUpfront RT groupInferior overall survivalCell lung cancerMutant lung adenocarcinomaEpidermal growth factor receptorCeritinib enables stereotactic radiosurgery to a previously untreatable symptomatic brain metastasis in a patient with ALK rearranged non-small cell lung cancer
Qian J, Yu J, Gettinger S, Chiang V. Ceritinib enables stereotactic radiosurgery to a previously untreatable symptomatic brain metastasis in a patient with ALK rearranged non-small cell lung cancer. Cancer Treatment And Research Communications 2016, 6: 17-19. DOI: 10.1016/j.ctrc.2016.02.002.Peer-Reviewed Original ResearchNon-small cell lung cancerAnaplastic lymphoma kinaseWhole-brain radiation therapySymptomatic brain metastasesBrain radiation therapyCell lung cancerBrain metastasesStereotactic radiosurgerySystemic therapyLung cancerRadiation therapyActive small-molecule tyrosine kinase inhibitorLarge symptomatic brain metastasisNext-generation ALK inhibitorsSmall molecule tyrosine kinase inhibitorsYear old Caucasian femaleMolecule tyrosine kinase inhibitorsGeneration ALK inhibitorsALK inhibitor crizotinibOld Caucasian femaleKey driver mutationsTyrosine kinase inhibitorsLocal therapyInhibitor crizotinibALK inhibitors