2018
Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors
Lopez Sambrooks C, Baro M, Quijano A, Narayan A, Cui W, Greninger P, Egan R, Patel A, Benes CH, Saltzman WM, Contessa JN. Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors. Cancer Research 2018, 78: canres.0505.2018. PMID: 30026325, PMCID: PMC6125176, DOI: 10.1158/0008-5472.can-18-0505.Peer-Reviewed Original ResearchConceptsMutant NSCLCMutant non-small cell lung cancerNon-small cell lung cancerSignificant tumor growth delayEGFR-TKI treatmentCell lung cancerTyrosine kinase inhibitor resistanceEGFR tyrosine kinase inhibitor resistanceLung cancer cell linesNGI-1Tumor growth delayEffective therapeutic targetCell linesKinase inhibitor resistanceTumor cell viabilityH1975 xenograftsCancer cell linesTKI treatmentComplex transmembrane proteinsEGFR-TKILung cancerTumor responseCell cycle arrestPreclinical modelsTherapeutic strategies
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 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
The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases
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. The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2016, 96: 406-413. PMID: 27598807, PMCID: PMC5575932, DOI: 10.1016/j.ijrobp.2016.06.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsErbB ReceptorsFemaleGenetic MarkersGenetic Predisposition to DiseaseHumansIncidenceLung NeoplasmsMaleMiddle AgedMutationPolymorphism, Single NucleotidePrevalenceProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesRetrospective StudiesRisk FactorsSurvival RateUnited StatesConceptsTyrosine kinase inhibitionBrain metastasesMedian survivalCause of deathGene alterationsDiagnosis of BMMulti-institutional retrospective databaseTKI-naïve patientsRisk of deathLonger median survivalKinase inhibitionALK gene alterationsTreatment patternsCancer mortalityLung cancerPrimary diagnosisRetrospective databaseCommon causeLung adenocarcinomaGroup overallPatientsFirst treatmentPrior trialsEGFRMonths
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