2020
Comprehensive T cell repertoire characterization of non-small cell lung cancer
Reuben A, Zhang J, Chiou SH, Gittelman RM, Li J, Lee WC, Fujimoto J, Behrens C, Liu X, Wang F, Quek K, Wang C, Kheradmand F, Chen R, Chow CW, Lin H, Bernatchez C, Jalali A, Hu X, Wu CJ, Eterovic AK, Parra ER, Yusko E, Emerson R, Benzeno S, Vignali M, Wu X, Ye Y, Little LD, Gumbs C, Mao X, Song X, Tippen S, Thornton RL, Cascone T, Snyder A, Wargo JA, Herbst R, Swisher S, Kadara H, Moran C, Kalhor N, Zhang J, Scheet P, Vaporciyan AA, Sepesi B, Gibbons DL, Robins H, Hwu P, Heymach JV, Sharma P, Allison JP, Baladandayuthapani V, Lee JJ, Davis MM, Wistuba II, Futreal PA, Zhang J. Comprehensive T cell repertoire characterization of non-small cell lung cancer. Nature Communications 2020, 11: 603. PMID: 32001676, PMCID: PMC6992630, DOI: 10.1038/s41467-019-14273-0.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerT cellsLung cancerAdoptive T-cell therapyEarly-stage NSCLC patientsT cell repertoire analysisT cell responsesLungs of patientsT-cell therapyNSCLC patientsInferior survivalClinicopathologic featuresImmune landscapeViral infectionSolid tumorsTherapeutic efficacyCell responsesCell therapyPatientsRepertoire analysisLungTumorsImmunotherapyConsiderable proportion
2018
Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC
Rolfo C, Mack PC, Scagliotti GV, Baas P, Barlesi F, Bivona TG, Herbst RS, Mok TS, Peled N, Pirker R, Raez LE, Reck M, Riess JW, Sequist LV, Shepherd FA, Sholl LM, Tan D, Wakelee HA, Wistuba II, Wynes MW, Carbone DP, Hirsch FR, Gandara DR. Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC. Journal Of Thoracic Oncology 2018, 13: 1248-1268. PMID: 29885479, DOI: 10.1016/j.jtho.2018.05.030.Peer-Reviewed Original ResearchConceptsLiquid biopsyAdvanced non-small cell lungClinical practiceNon-small cell lungResistance mutationsAdvanced NSCLC patientsTumor DNA (ctDNA) assaysCurrent available evidenceCell-free tumor DNALiquid biopsy approachesMultiple cancer typesNSCLC patientsClinical outcomesCell lungLung cancerThoracic oncologyClinical managementMultidisciplinary panelBiopsy approachUnmet needBiopsyPatient careStatement paperTumor DNATumor samples
2017
Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers
Nilsson MB, Sun H, Diao L, Tong P, Liu D, Li L, Fan Y, Poteete A, Lim SO, Howells K, Haddad V, Gomez D, Tran H, Pena GA, Sequist LV, Yang JC, Wang J, Kim ES, Herbst R, Lee JJ, Hong WK, Wistuba I, Hung MC, Sood AK, Heymach JV. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Science Translational Medicine 2017, 9 PMID: 29118262, PMCID: PMC5870120, DOI: 10.1126/scitranslmed.aao4307.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAfatinibAMP-Activated Protein Kinase KinasesCarcinoma, Non-Small-Cell LungCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmEpinephrineErbB ReceptorsHumansInterleukin-6Lung NeoplasmsMutationNorepinephrineProtein Kinase CProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptors, Adrenergic, betaSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerEGFR inhibitor resistanceΒ-blockersInhibitor resistanceStress hormonesLiver kinase B1Epidermal growth factor receptor tyrosine kinase inhibitor resistanceLower IL-6 concentrationsΒ-blocker useIL-6 concentrationsIL-6 inhibitionCell lung cancerTyrosine kinase inhibitor resistanceEGFR-TKI resistanceInterleukin-6 expressionKinase inhibitor resistanceChronic stress hormonesNSCLC patientsEGFR-TKIIL-6Lung cancerAR activationWorse outcomesNSCLC cellsTKI resistanceCirculating tumor DNA (ctDNA) to monitor treatment response and progression in patients treated with tyrosine kinase inhibitors (TKIs) and immunotherapy for EGFR-mutant non-small cell lung cancer (NSCLC).
Henick B, Goldberg S, Narayan A, Rossi C, Rodney S, Kole A, Politi K, Gettinger S, Herbst R, Patel A. Circulating tumor DNA (ctDNA) to monitor treatment response and progression in patients treated with tyrosine kinase inhibitors (TKIs) and immunotherapy for EGFR-mutant non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2017, 35: e20652-e20652. DOI: 10.1200/jco.2017.35.15_suppl.e20652.Peer-Reviewed Original ResearchNon-small cell lung cancerTyrosine kinase inhibitorsEGFR-mutant non-small cell lung cancerCtDNA levelsDisease progressionRadiographic progressionTKI therapyEGFR mutationsEGFR mutation-positive non-small cell lung cancerMutation-positive non-small cell lung cancerT790MAnti-PD-1 monotherapyEGFR mutation-positive patientsPD-1 inhibitor monotherapyEGFR-mutant NSCLC patientsSubset of patientsCell lung cancerMutation-positive patientsAssessment of responseLow ctDNA levelsChart reviewClinical characteristicsDurable responsesInhibitor monotherapyNSCLC patientsInterplay between immune infiltration and tumor progression and survival in non-small cell lung cancer: An analysis of institutional and public data.
Jalali A, Wang J, Lee W, Zhang J, Wu C, Gibbons D, Tang X, Kalhor N, Izzo J, Behrens C, Fossella F, Tsao A, Lee J, Swisher S, Heymach J, Futreal A, Wistuba I, Herbst R, Papadimitrakopoulou V, Zhang J. Interplay between immune infiltration and tumor progression and survival in non-small cell lung cancer: An analysis of institutional and public data. Journal Of Clinical Oncology 2017, 35: 8538-8538. DOI: 10.1200/jco.2017.35.15_suppl.8538.Peer-Reviewed Original ResearchNon-small cell lung cancerImmune infiltration scoreTumor immune infiltrationCell lung cancerImmune infiltrationLung cancerImmune responseAdvanced non-small cell lung cancerStage I/II diseaseTumor progressionStage I/IIStage III/IVInfiltration of tumorsInflammatory cell countsHigher median survivalLung Cancer ProjectPrimary tumor specimensLung adenocarcinoma samplesTypes of cancerMeans of CD3Tumor coreEstimate packageMedian survivalNSCLC patientsClinical outcomesP2.03b-053 Role of KRAS Mutation Status in NSCLC Patients Treated on SWOG S0819, a Phase III Trial of Chemotherapy with or without Cetuximab Topic: Biomarkers
Mack P, Moon J, Herbst R, Kim E, Semrad T, Redman M, Tsai R, Solis L, Gregg J, Hatcher S, Varella-Garcia M, Hirsch F, Blanke C, Kelly K, Gandara D. P2.03b-053 Role of KRAS Mutation Status in NSCLC Patients Treated on SWOG S0819, a Phase III Trial of Chemotherapy with or without Cetuximab Topic: Biomarkers. Journal Of Thoracic Oncology 2017, 12: s967-s968. DOI: 10.1016/j.jtho.2016.11.1334.Peer-Reviewed Original Research
2016
480TiP IMpower110: Phase III study on 1L atezolizumab (atezo) in PD-L1–selected chemotherapy (chemo)-naive NSCLC patients (pts)
De Marinis F, Jassem J, Spigel D, Lam S, Mocci S, Sandler A, Lopez-Chavez A, Deng Y, Giaccone G, Herbst R. 480TiP IMpower110: Phase III study on 1L atezolizumab (atezo) in PD-L1–selected chemotherapy (chemo)-naive NSCLC patients (pts). Annals Of Oncology 2016, 27 DOI: 10.1093/annonc/mdw594.044.Peer-Reviewed Original Research480TiP IMpower110: Phase III study on 1L atezolizumab (atezo) in PD-L1–selected chemotherapy (chemo)-naive NSCLC patients (pts)
De Marinis F, Jassem J, Spigel D, Lam S, Mocci S, Sandler A, Lopez-Chavez A, Deng Y, Giaccone G, Herbst R. 480TiP IMpower110: Phase III study on 1L atezolizumab (atezo) in PD-L1–selected chemotherapy (chemo)-naive NSCLC patients (pts). Annals Of Oncology 2016, 27: ix154. DOI: 10.1016/s0923-7534(21)00638-4.Peer-Reviewed Original Research
2015
A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies
Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer 2015, 15: 171. PMID: 25881079, PMCID: PMC4412099, DOI: 10.1186/s12885-015-1146-8.Peer-Reviewed Original ResearchConceptsGene copy number gainCopy number gainsRET rearrangementsTumor samplesComparator armVandetanib treatmentNumber gainRandomized phase III studyPhase III clinical trialsCell lung cancer trialsObjective response ratePhase III studyLung cancer trialsRET protein expressionNSCLC subpopulationVandetanib armRadiologic evidenceIII studyNSCLC patientsObjective responseTumor shrinkageComparator drugsCancer trialsClinical trialsRetrospective analysis
2014
B7-H1/PD-1 Blockade Therapy in Non–Small Cell Lung Cancer
Gettinger S, Herbst RS. B7-H1/PD-1 Blockade Therapy in Non–Small Cell Lung Cancer. The Cancer Journal 2014, 20: 281-289. PMID: 25098289, DOI: 10.1097/ppo.0000000000000063.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerPhase III trialsCell lung cancerIII trialsPD-1Lung cancerClinical trialsPD-1/PD-L1 inhibitorsB7-H1/PDTumor PD-L1 expressionSevere autoimmune toxicityChemotherapy-naive patientsPD-L1 expressionPotential of immunotherapyPD-L1 inhibitorsDeath ligand 1Future clinical trialsNumber of antibodiesAutoimmune toxicityExpansion cohortBlockade therapyDurable responsesNSCLC patientsStandard therapy
2012
Clinical Outcomes and Biomarker Profiles of Elderly Pretreated NSCLC Patients from the BATTLE Trial
Tsao AS, Liu S, Lee JJ, Alden C, Blumenschein G, Herbst R, Davis SE, Kim E, Lippman S, Stewart D, Tang XM, Wistuba I, Hong WK. Clinical Outcomes and Biomarker Profiles of Elderly Pretreated NSCLC Patients from the BATTLE Trial. Journal Of Thoracic Oncology 2012, 7: 1645-1652. PMID: 23059780, PMCID: PMC5161038, DOI: 10.1097/jto.0b013e31826910ff.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBexaroteneBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDrug Resistance, NeoplasmErlotinib HydrochlorideFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingNiacinamidePhenylurea CompoundsPiperidinesPrognosisQuinazolinesRetrospective StudiesSalvage TherapySorafenibSurvival RateTetrahydronaphthalenesConceptsProgression-free survivalDisease control rateNSCLC patientsOverall survivalElderly menGrade 3Older womenOlder menBetter median progression-free survivalHigher disease control rateLung Cancer Elimination (BATTLE) trialMedian progression-free survivalAge groupsBetter progression-free survivalCell lung cancer patientsBiomarker-Integrated ApproachesBiopsy-related pneumothoraxElderly NSCLC patientsMore grade 3Treatment-related deathsTumor tissue biomarkersRetrospective subgroup analysisSubset of patientsHigher overall survivalLung cancer patients
2011
The BATTLE Trial: Personalizing Therapy for Lung Cancer
Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GR, Tsao A, Stewart DJ, Hicks ME, Erasmus J, Gupta S, Alden CM, Liu S, Tang X, Khuri FR, Tran HT, Johnson BE, Heymach JV, Mao L, Fossella F, Kies MS, Papadimitrakopoulou V, Davis SE, Lippman SM, Hong WK. The BATTLE Trial: Personalizing Therapy for Lung Cancer. Cancer Discovery 2011, 1: 44-53. PMID: 22586319, PMCID: PMC4211116, DOI: 10.1158/2159-8274.cd-10-0010.Peer-Reviewed Original ResearchConceptsLung cancer patientsCancer patientsNon-small cell lung cancer patientsLung Cancer Elimination (BATTLE) trialCell lung cancer patientsDisease control rateCore needle biopsy specimensLung cancer clinical trialsSpecific patient populationsLung cancer therapyNeedle biopsy specimensCancer clinical trialsRelevant molecular biomarkersKRAS patientsNSCLC patientsPatient populationRandomization periodControl rateLaboratory findingsLung cancerBiopsy specimensClinical trialsTargeted therapyBATTLE TrialIndividualized treatmentDo elderly chemorefractory NSCLC patients derive benefit from salvage targeted therapy? Subgroup analysis of clinical outcome and toxicity from the BATTLE trial.
Tsao A, Liu S, Lee J, Alden C, Kim E, Blumenschein G, Herbst R, Lippman S, Wistuba I, Hong W. Do elderly chemorefractory NSCLC patients derive benefit from salvage targeted therapy? Subgroup analysis of clinical outcome and toxicity from the BATTLE trial. Journal Of Clinical Oncology 2011, 29: 7550-7550. DOI: 10.1200/jco.2011.29.15_suppl.7550.Peer-Reviewed Original Research
2010
BATTLE (Biomarker-based Approach of Targeted Therapy for Lung Cancer Elimination)
Hong W, Herbst R, Kim E. BATTLE (Biomarker-based Approach of Targeted Therapy for Lung Cancer Elimination). 2010 DOI: 10.21236/ada542458.Peer-Reviewed Original Research
2009
VeriStrat® classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab
Carbone DP, Salmon JS, Billheimer D, Chen H, Sandler A, Roder H, Roder J, Tsypin M, Herbst RS, Tsao AS, Tran HT, Dang TP. VeriStrat® classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab. Lung Cancer 2009, 69: 337-340. PMID: 20036440, PMCID: PMC2891357, DOI: 10.1016/j.lungcan.2009.11.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungDisease ProgressionDisease-Free SurvivalErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMass SpectrometryMiddle AgedNeoplasm Recurrence, LocalPrecision MedicinePredictive Value of TestsProteomeQuinazolinesConceptsNon-small cell lung cancer patientsCell lung cancer patientsAdvanced NSCLC patientsCombination of erlotinibLung cancer patientsToxic regimenNSCLC patientsPretreatment serumCancer patientsWorse outcomesProteomic classifierBlinded mannerPatientsErlotinibBevacizumabVeriStratSurvivalTreatmentRegimenProgressionSerumSWOG S0342 and S0536: Expression of EGFR protein and markers of epithelial-mesenchymal transformation (EMT) in cetuximab/chemotherapy-treated non-small cell lung cancer (NSCLC)
Franklin W, Gandara D, Kim E, Herbst R, Moon J, Redman M, Olsen C, Hirsch F, Mack P, Kelly K. SWOG S0342 and S0536: Expression of EGFR protein and markers of epithelial-mesenchymal transformation (EMT) in cetuximab/chemotherapy-treated non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2009, 27: 11076-11076. DOI: 10.1200/jco.2009.27.15_suppl.11076.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalShorter progression-free survivalEpithelial-mesenchymal transformationH-scoreEGFR proteinCell lung cancerKaplan-Meier plotsAggressive biological behaviorEGFR gene copy numberEMT marker vimentinHigh EGFR gene copy numberEGFR protein expressionNSCLC ptsNSCLC patientsOverall survivalTKI therapyEfficacy parametersLung cancerEGFR levelsEMT markersEGFR protein levelsMarker vimentinPT outcomesImmunoperoxidase method
2008
Increased EGFR Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non–Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy
Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, Franklin WA, Bunn PA, Varella-Garcia M, Gandara DR. Increased EGFR Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non–Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy. Journal Of Clinical Oncology 2008, 26: 3351-3357. PMID: 18612151, PMCID: PMC3368372, DOI: 10.1200/jco.2007.14.0111.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnalysis of VarianceAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCetuximabFemaleGene Expression Regulation, NeoplasticGenes, erbB-1HumansIn Situ HybridizationIn Situ Hybridization, FluorescenceLung NeoplasmsMaleMiddle AgedMultivariate AnalysisNeoplasm StagingPatient SelectionPredictive Value of TestsPrognosisProportional Hazards ModelsReference ValuesRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsCell lung cancer patientsLung cancer patientsFISH-negative patientsEGFR FISHNSCLC patientsCancer patientsSurvival timeMedian progression-free survival timeProgression-free survival timeEGFR tyrosine kinase inhibitorsDisease control rateChemotherapy-naive patientsAdvanced-stage NSCLCMedian survival timeEpidermal growth factor receptor (EGFR) gene copy numberFISH-positive patientsAvailable tumor tissueEGFR gene copy numberTyrosine kinase inhibitorsFISH-positive tumorsPhase II selection trialFISH-positive groupConcurrent chemotherapyConcurrent therapyPredictive factors
2007
Clinical implications of tumor cavitation following therapy with angiogenesis inhibitors in non-small cell lung cancer (NSCLC) patients
Onn A, Martinez C, Herbst R, Riddle J, Blumenschein G, Stewart D, Marom E. Clinical implications of tumor cavitation following therapy with angiogenesis inhibitors in non-small cell lung cancer (NSCLC) patients. Journal Of Clinical Oncology 2007, 25: 18034-18034. DOI: 10.1200/jco.2007.25.18_suppl.18034.Peer-Reviewed Original ResearchTumor cavitationLung cancer patientsAntiangiogenic agentsCancer patientsAngiogenesis inhibitorsNon-small cell lung cancer patientsClinical implicationsMedian progression-free survivalCell lung cancer patientsMD Anderson Cancer CenterProgression-free survivalSoft tissue densityAnderson Cancer CenterPrevious chemotherapyStable diseaseAdverse eventsNSCLC patientsAdvanced cancerCancer CenterNSCLC casesLung cancerPrimary tumorMedical recordsSubsegmental arteriesClinical data
2005
Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib
Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Jänne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ. Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib. Journal Of Clinical Oncology 2005, 23: 5900-5909. PMID: 16043828, DOI: 10.1200/jco.2005.02.857.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungCombined Modality TherapyDNA Mutational AnalysisErbB ReceptorsErlotinib HydrochlorideFemaleGenes, rasHumansLung NeoplasmsMaleMiddle AgedPaclitaxelPlacebosPredictive Value of TestsPrognosisQuinazolinesSurvival AnalysisTreatment OutcomeConceptsRetrospective subset analysisCell lung cancerEGFR mutationsKRAS mutationsLung cancerSubset analysisSingle-agent EGFR inhibitorsEpidermal growth factor receptor (EGFR) mutationsEGFR inhibitorsErlotinib-treated patientsFirst-line chemotherapyAdvanced NSCLC patientsChemotherapy-treated patientsPositive prognostic factorPoor clinical outcomeEGFR inhibitor treatmentImproved response ratesKRAS-mutant NSCLCKRAS exon 2Epidermal growth factor receptorGrowth factor receptorAdvanced NSCLCUntreated patientsNSCLC patientsPrognostic factorsClinically Meaningful Improvement in Symptoms and Quality of Life for Patients With Non-Small-Cell Lung Cancer Receiving Gefitinib in a Randomized Controlled Trial
Cella D, Herbst RS, Lynch TJ, Prager D, Belani CP, Schiller JH, Heyes A, Ochs JS, Wolf MK, Kay AC, Kris MG, Natale RB. Clinically Meaningful Improvement in Symptoms and Quality of Life for Patients With Non-Small-Cell Lung Cancer Receiving Gefitinib in a Randomized Controlled Trial. Journal Of Clinical Oncology 2005, 23: 2946-2954. PMID: 15699477, DOI: 10.1200/jco.2005.05.153.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDose-Response Relationship, DrugDouble-Blind MethodEndpoint DeterminationFemaleGefitinibHealth StatusHumansLung NeoplasmsMaleMiddle AgedQuality of LifeQuinazolinesSensitivity and SpecificitySurvival AnalysisConceptsLung Cancer SubscaleSymptom improvementTumor responseQuality of lifeCancer Therapy-Lung (FACT-L) questionnairePivotal phase II trialMedian overall survival timeCoprimary end pointsPrior chemotherapy regimensProtocol-specified analysisSymptom improvement ratePhase II trialBetter overall survivalCell lung cancerOverall survival timeGefitinib 250Radiographic regressionChemotherapy regimensStable diseaseII trialMost patientsOverall survivalRadiographic responseSymptomatic patientsNSCLC patients