2023
MA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC
Gettinger S, Goldberg S, Chiang A, Wilson F, Kim S, Rowen E, Gerrish H, Duffield E, Davies M, Dest V, Jackson R, Pope J, Myint H, Langermann S, Cheng W, Rimm D, Chen L, Herbst R. MA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC. Journal Of Thoracic Oncology 2023, 18: s155. DOI: 10.1016/j.jtho.2023.09.224.Peer-Reviewed Original ResearchNovel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG)
Lee S, Fan W, Wang A, Vaidya R, Redman M, Gettinger S, Bazhenova L, Herbst R, Hershman D, Unger J. Novel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG). JCO Clinical Cancer Informatics 2023, 7: e2200165. PMID: 37084329, PMCID: PMC10281446, DOI: 10.1200/cci.22.00165.Peer-Reviewed Original ResearchConceptsSystem organ classAdverse event dataRandomized phase III trialPhase III trialsCell lung cancerOncology clinical trialsOverall toxicity profileIII trialsNeurologic toxicityTreatment armsCardiac toxicityLung cancerClinical trialsGrade 3High prevalenceOrgan classToxicity profileNivolumabTreatment groupsStage IVEndocrine toxicityType of AEToxicity typesAE termsIpilimumabQuality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I
Unger J, Qian L, Redman M, Tavernier S, Minasian L, Sigal E, Papadimitrakopoulou V, Leblanc M, Cleeland C, Dzingle S, Summers T, Chao H, Madhusudhana S, Villaruz L, Crawford J, Gray J, Kelly K, Gandara D, Bazhenova L, Herbst R, Gettinger S, Moinpour C. Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I. Journal Of The National Cancer Institute 2023, 115: 437-446. PMID: 36625510, PMCID: PMC10086628, DOI: 10.1093/jnci/djad003.Peer-Reviewed Original ResearchConceptsQuality of lifeComposite risk modelAppetite lossSeverity scoreWeek 13Advanced squamous cell lung cancerWeek 7Baseline patient-reported outcomesRandomized phase III trialSquamous cell lung cancerPhase III trialsRisk of progressionShortness of breathCell lung cancerPatient-reported outcomesRisk of deathMultivariable linear regressionEffect of treatmentEvaluable patientsPrimary endpointIII trialsOverall survivalMedian ageAdvanced cancerPrognostic relevance
2022
Dynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab.
Gonzalez-Kozlova E, Huang H, Redman M, Herbst R, Gettinger S, Bazhenova L, Xie H, Patel M, Nie K, Harris J, Argueta K, Cerami E, Hong J, Biswas R, Van Nostrand S, Kelly K, Moravec R, Del Valle D, Kim-Schulze S, Gnjatic S. Dynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab. Journal Of Clinical Oncology 2022, 40: 9044-9044. DOI: 10.1200/jco.2022.40.16_suppl.9044.Peer-Reviewed Original ResearchImmune checkpoint blockadeSerial blood specimensObjective responseOverall survivalLung cancerBlood specimensCox modelRecurrent squamous cell lung cancerWk 3Randomized phase III trialSquamous cell lung cancerPhase III trialsBest objective responseCell lung cancerRisk of deathProtein levelsSerum analyte levelsIndicators of outcomeLinear mixed modelsSerum protein levelsProximity extension assayMeasurement of bloodEligible patientsLower IL6Checkpoint blockadeMultiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial.
Parra E, Duose D, Zhang J, Redman M, Segura R, Marques-Piubelli M, Fernandez C, Zhang B, Lindsay J, Moravec R, Kannan K, Luthra R, Alatrash G, Herbst R, Wistuba I, Gettinger S, Bazhenova L, Lee J, Zhang J, Haymaker C. Multiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial. Journal Of Clinical Oncology 2022, 40: 9046-9046. DOI: 10.1200/jco.2022.40.16_suppl.9046.Peer-Reviewed Original ResearchImmune checkpoint blockadeSquamous cell carcinomaT cellsBetter PFSLung cancerRecurrent squamous cell lung cancerTumor compartmentsLog-rank test analysisMetastatic lung squamous cell carcinomaSquamous cell lung cancerPD-1/CTLALung squamous cell carcinomaImmune cell scoreSingle-agent nivolumabDurable clinical benefitCD8 T cellsCell lung cancerCytotoxic immune cellsPositive clinical outcomesCell phenotypeFFPE tumor tissueBetter OSEligible patientsImmunogenomic profilingWorse OSNivolumab Plus Ipilimumab for Previously Treated Stage IV Squamous Cell Lung Cancer—Reply
Gettinger S, Redman MW, Herbst RS. Nivolumab Plus Ipilimumab for Previously Treated Stage IV Squamous Cell Lung Cancer—Reply. JAMA Oncology 2022, 8: 1-1. PMID: 35142793, DOI: 10.1001/jamaoncol.2021.7790.Peer-Reviewed Original Research
2021
Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer
Gettinger SN, Redman MW, Bazhenova L, Hirsch FR, Mack PC, Schwartz LH, Bradley JD, Stinchcombe TE, Leighl NB, Ramalingam SS, Tavernier SS, Yu H, Unger JM, Minichiello K, Highleyman L, Papadimitrakopoulou VA, Kelly K, Gandara DR, Herbst RS. Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer. JAMA Oncology 2021, 7: 1368-1377. PMID: 34264316, PMCID: PMC8283667, DOI: 10.1001/jamaoncol.2021.2209.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerInvestigator-assessed progression-free survivalNivolumab/ipilimumabPlatinum-based chemotherapyCell lung cancerOverall survivalIpilimumab groupLung cancerClinical trialsDisease progressionStage IV squamous cell lung cancerAdvanced non-small cell lung cancerHigher treatment-related adverse eventsTreatment-related adverse eventsSquamous cell lung cancerNational Clinical Trials NetworkStandard platinum-based chemotherapyEnd pointAddition of ipilimumabIntolerable toxic effectsNivolumab Plus IpilimumabMedian response durationPrimary end pointSecondary end pointsProgression-free survivalOA01.04 Tumor Mutation Burden (TMB) by Next Generation Sequencing (NGS) Associates with Survival (OS) in Lung-MAP Immunotherapy Trials S1400I and S1400A
Hirsch F, Hua X, Wu M, Neal J, Cheng H, Gettinger S, Bazhenova L, Papadimitrakopoulou V, Borghaei H, Mack P, Kelly K, Herbst R, Gandara D, Redman M, Kozono D. OA01.04 Tumor Mutation Burden (TMB) by Next Generation Sequencing (NGS) Associates with Survival (OS) in Lung-MAP Immunotherapy Trials S1400I and S1400A. Journal Of Thoracic Oncology 2021, 16: s102. DOI: 10.1016/j.jtho.2021.01.273.Peer-Reviewed Original Research
2020
Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403.
Goldberg SB, Redman MW, Lilenbaum R, Politi K, Stinchcombe TE, Horn L, Chen EH, Mashru SH, Gettinger SN, Melnick MA, Herbst RS, Baumgart MA, Miao J, Moon J, Kelly K, Gandara DR. Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403. Journal Of Clinical Oncology 2020, 38: 4076-4085. PMID: 33021871, PMCID: PMC7768342, DOI: 10.1200/jco.20.01149.Peer-Reviewed Original ResearchConceptsProgression-free survivalLung cancerMutant NSCLCEGFR monoclonal antibody cetuximabSmall cell lung cancerAddition of cetuximabPrimary end pointTyrosine kinase inhibitor afatinibCell lung cancerEGFR-Mutant NonCombination of afatinibMonoclonal antibody cetuximabAdvanced diseaseAdverse eventsOverall survivalMulticenter trialLine treatmentEGFR-TKIAntibody cetuximabDose reductionInhibitor afatinibInterim analysisCetuximabInsufficient evidencePatientsBiomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling
Zugazagoitia J, Gupta S, Liu Y, Fuhrman K, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling. Clinical Cancer Research 2020, 26: 4360-4368. PMID: 32253229, PMCID: PMC7442721, DOI: 10.1158/1078-0432.ccr-20-0175.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-1 checkpoint blockadeCell lung cancerCheckpoint blockadeLung cancerAdvanced non-small cell lung cancerUnivariate unadjusted analysisProgression-free survivalImmune cell countsMinority of patientsRobust predictive biomarkersBiomarkers of responseLarge independent cohortsSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyOverall survivalClinical outcomesImmune predictorsHigher CD56NSCLC casesPredictive biomarkersUnadjusted analysesImmune parametersTissue microarrayPembrolizumab 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 ResearchConceptsBrain 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 CriteriaImmune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations
Remon J, Passiglia F, Ahn MJ, Barlesi F, Forde PM, Garon EB, Gettinger S, Goldberg SB, Herbst RS, Horn L, Kubota K, Lu S, Mezquita L, Paz-Ares L, Popat S, Schalper KA, Skoulidis F, Reck M, Adjei AA, Scagliotti GV. Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations. Journal Of Thoracic Oncology 2020, 15: 914-947. PMID: 32179179, DOI: 10.1016/j.jtho.2020.03.006.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsThoracic malignanciesCheckpoint inhibitorsThymic carcinomaDeath ligand 1 (PD-L1) immune checkpoint inhibitorsAnti-programmed cell death protein 1Cell death protein 1/T-lymphocyte antigen 4 antibodyCombination of ICIsDeath protein 1/Long-term survival benefitHost antitumor immune responseCell death protein 1Immune evasion processStage III NSCLCAntitumor immune responseEarly-stage diseaseDeath protein 1Portion of patientsMalignant pleural mesotheliomaOptimal treatment durationFuture treatment strategiesDefinitive clinical benefitFuture therapeutic developmentAvailable scientific evidenceImmune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapy
2019
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomesOA04.01 A Phase III Randomized Study of Nivolumab/Ipilimumab vs Nivolumab for Previously Treated Stage IV Squamous Cell Lung Cancer
Bazhenova L, Redman M, Gettinger S, Hirsch F, Mack P, Schwartz L, Gandara D, Bradley J, Stinchcombe T, Leighl N, Ramalingam S, Tavernier S, Minichiello K, Kelly K, Papadimitrakopoulou V, Herbst R. OA04.01 A Phase III Randomized Study of Nivolumab/Ipilimumab vs Nivolumab for Previously Treated Stage IV Squamous Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: s214. DOI: 10.1016/j.jtho.2019.08.423.Peer-Reviewed Original ResearchExpression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis
Datar I, Sanmamed MF, Wang J, Henick BS, Choi J, Badri T, Dong W, Mani N, Toki M, Mejías L, Lozano MD, Perez-Gracia JL, Velcheti V, Hellmann MD, Gainor JF, McEachern K, Jenkins D, Syrigos K, Politi K, Gettinger S, Rimm DL, Herbst RS, Melero I, Chen L, Schalper KA. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis. Clinical Cancer Research 2019, 25: 4663-4673. PMID: 31053602, PMCID: PMC7444693, DOI: 10.1158/1078-0432.ccr-18-4142.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDBiomarkers, TumorCarcinoma, Non-Small-Cell LungGene Expression Regulation, NeoplasticHepatitis A Virus Cellular Receptor 2HumansLung NeoplasmsLymphocyte ActivationLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingPrognosisProgrammed Cell Death 1 ReceptorRetrospective StudiesSingle-Cell AnalysisSurvival RateConceptsNon-small cell lung cancerHuman non-small cell lung cancerTumor-infiltrating lymphocytesAdvanced non-small cell lung cancerTim-3PD-1Cell lung cancerLAG-3Lung cancerPD-1 axis blockadeShorter progression-free survivalBaseline samplesTim-3 protein expressionMajor clinicopathologic variablesMultiplexed quantitative immunofluorescencePD-1 expressionProgression-free survivalTim-3 expressionLAG-3 expressionT-cell phenotypeTumor mutational burdenImmune inhibitory receptorsImmune evasion pathwaysTIM-3 proteinMass cytometry analysisA phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952).
Bazhenova L, Redman M, Gettinger S, Hirsch F, Mack P, Schwartz L, Gandara D, Bradley J, Stinchcombe T, Leighl N, Ramalingam S, Tavernier S, Minichiello K, Kelly K, Papadimitrakopoulou V, Herbst R. A phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952). Journal Of Clinical Oncology 2019, 37: 9014-9014. DOI: 10.1200/jco.2019.37.15_suppl.9014.Peer-Reviewed Original ResearchInvestigator-assessed progression-free survivalOverall survivalInterim analysisStage IV squamous cell lung cancerSquamous cell lung cancerGrade 5 AEsImmunotherapy-naïve patientsStudies of nivolumabTreatment-related AEsPD-L1 expressionProgression-free survivalPhase IIICell lung cancerECOG 0Primary endpointRECIST 1.1Baseline characteristicsPD-L1Lung cancerLung-MAPNivolumabStage IVPatientsResponse rateMaster protocolsEGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer
Hastings K, Yu HA, Wei W, Sanchez-Vega F, DeVeaux M, Choi J, Rizvi H, Lisberg A, Truini A, Lydon CA, Liu Z, Henick BS, Wurtz A, Cai G, Plodkowski AJ, Long NM, Halpenny DF, Killam J, Oliva I, Schultz N, Riely GJ, Arcila ME, Ladanyi M, Zelterman D, Herbst RS, Goldberg SB, Awad MM, Garon EB, Gettinger S, Hellmann MD, Politi K. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer. Annals Of Oncology 2019, 30: 1311-1320. PMID: 31086949, PMCID: PMC6683857, DOI: 10.1093/annonc/mdz141.Peer-Reviewed Original ResearchMeSH KeywordsAgedAllelesAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErbB ReceptorsFemaleGenetic HeterogeneityHumansLungLung NeoplasmsMaleMiddle AgedMutationProgrammed Cell Death 1 ReceptorProgression-Free SurvivalRetrospective StudiesTobacco SmokingConceptsEGFR-mutant tumorsMemorial Sloan-Kettering Cancer CenterYale Cancer CenterImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint blockadeTumor mutation burdenCancer CenterLung tumorsCheckpoint blockadeEGFR mutant lung tumorsMutant tumorsCheckpoint inhibitorsLung cancerMutation burdenImmune checkpoint blockade treatmentLow tumor mutation burdenDana-Farber Cancer InstituteEGFR wild-type lung cancersCheckpoint blockade treatmentCell lung cancerEGFR mutation subtypesSimilar smoking historyCell death 1Lung cancer casesExpression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC)
Carvajal-Hausdorf D, Altan M, Velcheti V, Gettinger SN, Herbst RS, Rimm DL, Schalper KA. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC). Journal For ImmunoTherapy Of Cancer 2019, 7: 65. PMID: 30850021, PMCID: PMC6408760, DOI: 10.1186/s40425-019-0540-1.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overB7 AntigensB7-H1 AntigenBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm GradingNeoplasm StagingPrognosisRetrospective StudiesSmall Cell Lung CarcinomaV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsSmall cell lung cancerCell lung cancerB7-H4B7-H3Lung cancerPD-L1Non-small cell lung cancerBackgroundSmall cell lung cancerAnti-tumor immune responseHuman small cell lung cancerQuantitative immunofluorescenceB7 family ligandsLevels of TILsMultiplexed quantitative immunofluorescenceLevels of CD3Effector T cellsImmune checkpoint blockersPromising clinical activityTissue microarray formatLymphocyte subsetsCheckpoint blockersOverall survivalLung malignancyClinicopathological variablesMarker levelsImmune Checkpoint Inhibitor–Associated Pericarditis
Altan M, Toki MI, Gettinger SN, Carvajal-Hausdorf DE, Zugazagoitia J, Sinard JH, Herbst RS, Rimm DL. Immune Checkpoint Inhibitor–Associated Pericarditis. Journal Of Thoracic Oncology 2019, 14: 1102-1108. PMID: 30851443, PMCID: PMC6617516, DOI: 10.1016/j.jtho.2019.02.026.Peer-Reviewed Original ResearchConceptsAdverse eventsCTLA-4 inhibitorsImmune checkpoint inhibitorsDeath-1/Pericardial window procedureCheckpoint inhibitorsThird patientClinical presentationCardiac toxicityHistopathologic findingsSide effectsPericarditisPatientsDeath ligandsPotential mechanismsWindow procedureInhibitorsImmunotherapyNSCLCCardiotoxicityAutopsiesTherapy