2022
Brain 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 microenvironmentMulticenter 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 ResearchMeSH KeywordsBrainBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsHumansLung NeoplasmsRadiosurgeryReceptor Protein-Tyrosine KinasesRetrospective StudiesConceptsNon-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 optionsGraded 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
Reirradiation 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 ResearchMeSH KeywordsBrain NeoplasmsCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsRadiosurgeryRe-IrradiationRetrospective StudiesConceptsLocal 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
Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial
Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Wilson FH, Omay SB, Yu JB, Jilaveanu L, Tran T, Pavlik K, Rowen E, Gerrish H, Komlo A, Gupta R, Wyatt H, Ribeiro M, Kluger Y, Zhou G, Wei W, Chiang VL, Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2020, 21: 655-663. PMID: 32251621, PMCID: PMC7380514, DOI: 10.1016/s1470-2045(20)30111-x.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, TumorBrain NeoplasmsCarcinoma, Non-Small-Cell LungFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisConceptsBrain metastasis responseYale Cancer CenterPD-L1 expressionPhase 2 trialUntreated brain metastasesBrain metastasesAdrenal insufficiencyAdverse eventsMetastasis responseCNS diseaseCancer CenterCohort 2Cohort 1Eastern Cooperative Oncology Group performance statusTreatment-related serious adverse eventsModified Response Evaluation CriteriaStage IV NSCLCTreatment-related deathsAcute kidney injuryPD-1 blockadeSerious adverse eventsSolid Tumors criteriaPhase 2 studyProportion of patientsResponse Evaluation Criteria
2019
Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy
Tran TT, Mahajan A, Chiang VL, Goldberg SB, Nguyen DX, Jilaveanu LB, Kluger HM. Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy. Journal For ImmunoTherapy Of Cancer 2019, 7: 200. PMID: 31362777, PMCID: PMC6668163, DOI: 10.1186/s40425-019-0684-z.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAntibodies, Monoclonal, HumanizedAntigens, CD34Antineoplastic Agents, ImmunologicalBlood-Brain BarrierBrain EdemaBrain NeoplasmsCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicDrug Administration ScheduleHumansLung NeoplasmsMelanomaRetrospective StudiesTight JunctionsTreatment OutcomeTumor Cells, CulturedConceptsMelanoma brain metastasesBrain metastasesPerilesional edemaVessel densityEdema volumeSensitive tumorsBlood-brain barrier model systemNon-small cell lungTight junction resistancePhase II clinical trialSignificant perilesional edemaUntreated brain metastasesBlood-brain barrierPre-clinical modelsDegree of edemaTumor mass effectPotential causesMelanoma brainShort-term cultureExtracranial metastasesImmune therapyMelanoma patientsSignificant morbidityCell lungLarge tumorsLocal 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
2017
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)
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 survivalReply to A. Chalmers et al
Magnuson WJ, Lester-Coll NH, Yu JB, Chiang VL. Reply to A. Chalmers et al. Journal Of Clinical Oncology 2017, 35: jco.2017.73.218. PMID: 28481709, DOI: 10.1200/jco.2017.73.2180.Peer-Reviewed Original ResearchBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsHumansLung NeoplasmsRetrospective StudiesManagement 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
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
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 cohortReply to M.S. Copur et al and to M.C. Chamberlain
Contessa JN, Johung KL, Goldberg S, Chiang VL. Reply to M.S. Copur et al and to M.C. Chamberlain. Journal Of Clinical Oncology 2016, 34: 2316-2317. PMID: 27114599, DOI: 10.1200/jco.2016.67.2816.Peer-Reviewed Original ResearchImpact 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 receptor
2015
Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis
Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, Ning MS, Attia A, Lovly CM, Goldberg S, Beal K, Yu JB, Kavanagh BD, Chiang VL, Camidge DR, Contessa JN. Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis. Journal Of Clinical Oncology 2015, 34: 123-129. PMID: 26438117, PMCID: PMC5070549, DOI: 10.1200/jco.2015.62.0138.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarbazolesCarcinoma, Non-Small-Cell LungCranial IrradiationCrizotinibDisease-Free SurvivalFemaleFollow-Up StudiesGene RearrangementHumansKaplan-Meier EstimateKarnofsky Performance StatusLung NeoplasmsMaleMiddle AgedMolecular Targeted TherapyNeoplasm StagingPiperidinesPrognosisProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyridinesPyrimidinesRadiosurgeryReceptor Protein-Tyrosine KinasesRisk AssessmentRisk FactorsSmokingSulfonesConceptsIntracranial progression-free survivalBrain metastasesProgression-free survivalPrognostic factorsLung cancerMedian intracranial progression-free survivalNon-small cell lung cancerTyrosine kinase inhibitor therapyProgressive brain metastasesRefinement of prognosisKarnofsky performance scorePercent of patientsClinical prognostic factorsPopulation of patientsSingle brain metastasisCell lung cancerKinase inhibitor therapyCox proportional hazardsMulti-institutional studyMedian OSExtracranial metastasesImproved survivalInhibitor therapyInitial treatmentMultivariable analysisEvolution of multidisciplinary brain metastasis management: case study and literature review.
Colaco R, Martin P, Chiang V. Evolution of multidisciplinary brain metastasis management: case study and literature review. The Yale Journal Of Biology And Medicine 2015, 88: 157-65. PMID: 26029014, PMCID: PMC4445437.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCarcinoma, Non-Small-Cell LungCase ManagementChemoradiotherapyCombined Modality TherapyFemaleHumansMiddle AgedPatient Care TeamRadiosurgeryTreatment OutcomeConceptsBrain metastasesManagement of BMProgression-free survivalLocal tumor controlLong-term survivorsNeurocognitive side effectsBrain metastasis managementSymptom reliefTumor burdenTumor controlCancer patientsTreatment modalitiesMetastasis managementSide effectsRadiation modalitiesFunctional independenceContemporary managementPatientsLiterature reviewSurvivalModalitiesOverall qualityCoordinated approachManagementPrognosis
2013
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Johung KL, Yao X, Li F, Yu JB, Gettinger SN, Goldberg S, Decker RH, Hess JA, Chiang VL, Contessa JN. A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer. Clinical Cancer Research 2013, 19: 5523-5532. PMID: 23897899, DOI: 10.1158/1078-0432.ccr-13-0836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsRadiation ToleranceReceptor Protein-Tyrosine KinasesRecurrenceTranslocation, GeneticTumor BurdenConceptsNon-small cell lung cancerCell lung cancerEML4-ALK translocationGamma knife treatmentLocal controlTumor genotypeLung cancerEGFR mutationsCox proportional hazards modelDistant brain controlDistant brain recurrenceGamma knife radiotherapyEGFR kinase domain mutationsSuperior local controlField local controlKRAS mutation statusProportional hazards modelKinase domain mutationsEGF receptorMetastasis sizeBrain recurrenceBrain metastasesField recurrenceClinical outcomesIndependent predictors
2009
Diagnosis-Specific Prognostic Factors, Indexes, and Treatment Outcomes for Patients With Newly Diagnosed Brain Metastases: A Multi-Institutional Analysis of 4,259 Patients
Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, Kirkpatrick J, Schwer A, Gaspar LE, Fiveash JB, Chiang V, Knisely J, Sperduto CM, Mehta M. Diagnosis-Specific Prognostic Factors, Indexes, and Treatment Outcomes for Patients With Newly Diagnosed Brain Metastases: A Multi-Institutional Analysis of 4,259 Patients. International Journal Of Radiation Oncology • Biology • Physics 2009, 77: 655-661. PMID: 19942357, DOI: 10.1016/j.ijrobp.2009.08.025.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedAnalysis of VarianceBrain NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellCombined Modality TherapyGastrointestinal NeoplasmsHumansKarnofsky Performance StatusKidney NeoplasmsLung NeoplasmsMelanomaMiddle AgedPrognosisRetrospective StudiesSelection BiasSkin NeoplasmsSmall Cell Lung CarcinomaTreatment OutcomeConceptsSignificant prognostic factorsKarnofsky performance statusDiagnosis-specific prognostic factorsNumber of BMSmall cell lung cancerBrain metastasesPrognostic factorsCell lung cancerLung cancerPerformance statusBM patientsRandomized trialsGastrointestinal cancerOnly significant prognostic factorRecurrent brain metastasesFuture randomized trialsRenal cell cancerDS-GPA scoreRenal cell carcinomaExtracranial metastasesMedian survivalCell cancerHistologic typePrognostic indexCell carcinoma
2006
Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases
DiLuna ML, King JT, Knisely JP, Chiang VL. Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer 2006, 109: 135-145. PMID: 17133440, DOI: 10.1002/cncr.22367.Peer-Reviewed Original ResearchMeSH KeywordsAgedBrain NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungEsophageal NeoplasmsFemaleHumansLung NeoplasmsMaleMelanomaMiddle AgedNeoplasmsPrognosisRadiosurgerySurvival RateConceptsSubgroup of patientsStereotactic radiosurgeryBreast cancerGamma Knife stereotactic radiosurgeryNonsmall cell lung carcinomaCommon tumor histologyInitial stereotactic radiosurgeryWhole brain radiationConnecticut Tumor RegistryMultivariate survival analysisTotal tumor volumeCell lung carcinomaBrain metastasesCerebral metastasesMedian survivalMetastasis locationMedian agePrognostic factorsTumor RegistryTumor histologyIntracranial metastasesPatient populationEsophageal cancerIndependent associationLung carcinoma