2023
Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆
Mok T, Lopes G, Cho B, Kowalski D, Kasahara K, Wu Y, de Castro G, Turna H, Cristescu R, Aurora-Garg D, Loboda A, Lunceford J, Kobie J, Ayers M, Pietanza M, Piperdi B, Herbst R. Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆. Annals Of Oncology 2023, 34: 377-388. PMID: 36709038, DOI: 10.1016/j.annonc.2023.01.011.Peer-Reviewed Original ResearchConceptsTissue tumor mutational burdenImproved overall survivalProgression-free survivalTumor mutational burdenOverall survivalKEYNOTE-042Pembrolizumab monotherapyKRAS mutationsClinical utilityMutational burdenMutation statusPD-L1 tumor proportion scoreStandard first-line treatmentEGFR/ALK alterationsAdvanced PD-L1First-line treatmentPD-L1 expressionTumor proportion scorePlatinum-based chemotherapyDeath ligand 1Cell lung cancerPotential predictive biomarkersCut pointsKRAS mutation statusRetrospective exploratory analysisInterplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19
Bakouny Z, Labaki C, Grover P, Awosika J, Gulati S, Hsu C, Alimohamed S, Bashir B, Berg S, Bilen M, Bowles D, Castellano C, Desai A, Elkrief A, Eton O, Fecher L, Flora D, Galsky M, Gatti-Mays M, Gesenhues A, Glover M, Gopalakrishnan D, Gupta S, Halfdanarson T, Hayes-Lattin B, Hendawi M, Hsu E, Hwang C, Jandarov R, Jani C, Johnson D, Joshi M, Khan H, Khan S, Knox N, Koshkin V, Kulkarni A, Kwon D, Matar S, McKay R, Mishra S, Moria F, Nizam A, Nock N, Nonato T, Panasci J, Pomerantz L, Portuguese A, Provenzano D, Puc M, Rao Y, Rhodes T, Riely G, Ripp J, Rivera A, Ruiz-Garcia E, Schmidt A, Schoenfeld A, Schwartz G, Shah S, Shaya J, Subbiah S, Tachiki L, Tucker M, Valdez-Reyes M, Weissmann L, Wotman M, Wulff-Burchfield E, Xie Z, Yang Y, Thompson M, Shah D, Warner J, Shyr Y, Choueiri T, Wise-Draper T, Fromowitz A, Gandhi R, Gartrell B, Goel S, Halmos B, Makower D, O' Sullivan D, Ohri N, Portes M, Shapiro L, Shastri A, Sica R, Verma A, Butt O, Campian J, Fiala M, Henderson J, Monahan R, Stockerl-Goldstein K, Zhou A, Bitran J, Hallmeyer S, Mundt D, Pandravada S, Papaioannou P, Patel M, Streckfuss M, Tadesse E, Gatson N, Kundranda M, Lammers P, Loree J, Yu I, Bindal P, Lam B, Peters M, Piper-Vallillo A, Egan P, Farmakiotis D, Arvanitis P, Klein E, Olszewski A, Vieira K, Angevine A, Bar M, Del Prete S, Fiebach M, Gulati A, Hatton E, Houston K, Rose S, Steve Lo K, Stratton J, Weinstein P, Garcia J, Routy B, Hoyo-Ulloa I, Dawsey S, Lemmon C, Pennell N, Sharifi N, Painter C, Granada C, Hoppenot C, Li A, Bitterman D, Connors J, Demetri G, Florez (Duma) N, Freeman D, Giordano A, Morgans A, Nohria A, Saliby R, Tolaney S, Van Allen E, Xu W, Zon R, Halabi S, Zhang T, Dzimitrowicz H, Leighton J, Graber J, Grivas P, Hawley J, Loggers E, Lyman G, Lynch R, Nakasone E, Schweizer M, Vinayak S, Wagner M, Yeh A, Dansoa Y, Makary M, Manikowski J, Vadakara J, Yossef K, Beckerman J, Goyal S, Messing I, Rosenstein L, Steffes D, Alsamarai S, Clement J, Cosin J, Daher A, Dailey M, Elias R, Fein J, Hosmer W, Jayaraj A, Mather J, Menendez A, Nadkarni R, Serrano O, Yu P, Balanchivadze N, Gadgeel S, Accordino M, Bhutani D, Bodin B, Hershman D, Masson C, Alexander M, Mushtaq S, Reuben D, Bernicker E, Deeken J, Jeffords K, Shafer D, Cárdenas A, Cuervo Campos R, De-la-Rosa-Martinez D, Ramirez A, Vilar-Compte D, Gill D, Lewis M, Low C, Jones M, Mansoor A, Mashru S, Werner M, Cohen A, McWeeney S, Nemecek E, Williamson S, Peters S, Smith S, Lewis G, Zaren H, Akhtari M, Castillo D, Cortez K, Lau E, Nagaraj G, Park K, Reeves M, O'Connor T, Altman J, Gurley M, Mulcahy M, Wehbe F, Durbin E, Nelson H, Ramesh V, Sachs Z, Wilson G, Bardia A, Boland G, Gainor J, Peppercorn J, Reynolds K, Rosovsky R, Zubiri L, Bekaii-Saab T, Joyner M, Riaz I, Senefeld J, Shah S, Ayre S, Bonnen M, Mahadevan D, McKeown C, Mesa R, Ramirez A, Salazar M, Shah P, Wang C, Bouganim N, Papenburg J, Sabbah A, Tagalakis V, Vinh D, Nanchal R, Singh H, Bahadur N, Bao T, Belenkaya R, Nambiar P, O’Cearbhaill R, Papadopoulos E, Philip J, Robson M, Rosenberg J, Wilkins C, Tamimi R, Cerrone K, Dill J, Faller B, Alomar M, Chandrasekhar S, Hume E, Islam J, Ajmera A, Brouha S, Cabal A, Choi S, Hsiao A, Jiang J, Kligerman S, Park J, Razavi P, Reid E, Bhatt P, Mariano M, Thomson C, Glace M, Knoble J, Rink C, Zacks R, Blau S, Brown C, Cantrell A, Namburi S, Polimera H, Rovito M, Edwin N, Herz K, Kennecke H, Monfared A, Sautter R, Cronin T, Elshoury A, Fleissner B, Griffiths E, Hernandez-Ilizaliturri F, Jain P, Kariapper A, Levine E, Moffitt M, O'Connor T, Smith L, Wicher C, Zsiros E, Jabbour S, Misdary C, Shah M, Batist G, Cook E, Ferrario C, Lau S, Miller W, Rudski L, Santos Dutra M, Wilchesky M, Mahmood S, McNair C, Mico V, Dixon B, Kloecker G, Logan B, Mandapakala C, Cabebe E, Jha A, Khaki A, Nagpal S, Schapira L, Wu J, Whaley D, Lopes G, de Cardenas K, Russell K, Stith B, Taylor S, Klamerus J, Revankar S, Addison D, Chen J, Haynam M, Jhawar S, Karivedu V, Palmer J, Pillainayagam C, Stover D, Wall S, Williams N, Abbasi S, Annis S, Balmaceda N, Greenland S, Kasi A, Rock C, Luders M, Smits M, Weiss M, Chism D, Owenby S, Ang C, Doroshow D, Metzger M, Berenberg J, Uyehara C, Fazio A, Huber K, Lashley L, Sueyoshi M, Patel K, Riess J, Borno H, Small E, Zhang S, Andermann T, Jensen C, Rubinstein S, Wood W, Ahmad S, Brownfield L, Heilman H, Kharofa J, Latif T, Marcum M, Shaikh H, Sohal D, Abidi M, Geiger C, Markham M, Russ A, Saker H, Acoba J, Choi H, Rho Y, Feldman L, Gantt G, Hoskins K, Khan M, Liu L, Nguyen R, Pasquinelli M, Schwartz C, Venepalli N, Vikas P, Zakharia Y, Friese C, Boldt A, Gonzalez C, Su C, Su C, Yoon J, Bijjula R, Mavromatis B, Seletyn M, Wood B, Zaman Q, Kaklamani V, Beeghly A, Brown A, Charles L, Cheng A, Crispens M, Croessmann S, Davis E, Ding T, Duda S, Enriquez K, French B, Gillaspie E, Hausrath D, Hennessy C, Lewis J, Li X, Prescott L, Reid S, Saif S, Slosky D, Solorzano C, Sun T, Vega-Luna K, Wang L, Aboulafia D, Carducci T, Goldsmith K, Van Loon S, Topaloglu U, Moore J, Rice R, Cabalona W, Cyr S, Barrow McCollough B, Peddi P, Rosen L, Ravindranathan D, Hafez N, Herbst R, LoRusso P, Lustberg M, Masters T, Stratton C. Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19. JAMA Oncology 2023, 9: 128-134. PMID: 36326731, PMCID: PMC9634600, DOI: 10.1001/jamaoncol.2022.5357.Peer-Reviewed Original ResearchConceptsCOVID-19 severitySystemic anticancer therapyWorse COVID-19 severityCytokine stormBaseline immunosuppressionCohort studyAnticancer therapyCOVID-19Registry-based retrospective cohort studyIntensive care unit admissionCare unit admissionRetrospective cohort studyMulti-institutional registryLaboratory-confirmed infectionSevere clinical outcomesImmune system activationSARS-CoV-2Non-Hispanic whitesCOVID-19 diagnosisIO therapyPrevious cancerUnit admissionSecondary outcomesMedian agePrimary outcome
2022
Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Henick BS, Villarroel-Espindola F, Datar I, Sanmamed MF, Yu J, Desai S, Li A, Aguirre-Ducler A, Syrigos K, Rimm DL, Chen L, Herbst RS, Schalper KA. Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005025. PMID: 35793873, PMCID: PMC9260844, DOI: 10.1136/jitc-2022-005025.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHLA-DR AntigensHumansLung NeoplasmsMyeloid CellsRetrospective StudiesConceptsNon-small cell lung cancerSquamous cell carcinomaHuman non-small cell lung cancerMyeloid cell subsetsCell lung cancerHLA-DRLung adenocarcinomaMyeloid cellsCell subsetsLung cancerLung tissueQuantitative immunofluorescenceNon-tumor lung tissuesIndependent NSCLC cohortsLevels of CD68Multiplexed quantitative immunofluorescenceProinflammatory myeloid cellsHLA-DR expressionM1-like macrophagesImmature myeloid cell populationMyeloid cell populationsKRAS mutant tumorsNormal lung tissuesTumor epithelial cellsNon-tumor lungProgrammed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC
Fernandez AI, Gavrielatou N, McCann L, Shafi S, Moutafi MK, Martinez-Morilla S, Vathiotis IA, Aung TN, Yaghoobi V, Bai Y, Chan YG, Weidler J, Herbst R, Bates M, Rimm DL. Programmed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC. Journal Of Thoracic Oncology 2022, 17: 1078-1085. PMID: 35764237, DOI: 10.1016/j.jtho.2022.06.007.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHigh negative predictive valueLow stage patientsICI therapyPD-L1Negative predictive valueAdjuvant settingLong-term benefitsPredictive valueProgrammed Death Ligand 1PD-L1 mRNA levelsCurrent predictive biomarkersHigh PD-L1Death ligand 1Lung cancer managementPD-L1 mRNAUseful objective methodReal-time reverse transcription-polymerase chain reactionMRNA levelsStandard of careReverse transcription-polymerase chain reactionQuantitative real-time reverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMRNA expression levelsAdvanced NSCLCRacial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer
Fu J, Reid S, French B, Hennessy C, Hwang C, Gatson N, Duma N, Mishra S, Nguyen R, Hawley J, Singh S, Chism D, Venepalli N, Warner J, Choueiri T, Schmidt A, Fecher L, Girard J, Bilen M, Ravindranathan D, Goyal S, Wise-Draper T, Park C, Painter C, McGlown S, de Lima Lopes G, Serrano O, Shah D, Halmos B, Verma A, Gartrell B, Goel S, Ohri N, Sica R, Thakkar A, Stockerl-Goldstein K, Butt O, Campian J, Fiala M, Monahan R, Zhou A, Patel J, Piper-Vallillo A, Bindal P, Thompson M, Bohachek P, Mundt D, Streckfuss M, Tadesse E, Lammers P, Panagiotou O, Egan P, Farmakiotis D, Khan H, Olszewski A, Loaiza-Bonilla A, Del Prete S, Angevine A, Bar M, Gulati A, Steve Lo K, Stratton J, Weinstein P, Caimi P, Barnholtz-Sloan J, Garcia J, Nakayama J, Gupta S, Pennell N, Ahluwalia M, Dawsey S, Lemmon C, Nizam A, Hoppenot C, Li A, Bakouny Z, Bouchard G, Busser F, Connors J, Curran C, Demetri G, Giordano A, Kelleher K, Nohria A, Shaw G, Van Allen E, Nuzzo P, Xu V, Zon R, Zhang T, Halabi S, Leighton J, Lyman G, Graber J, Grivas P, Khaki A, Loggers E, Lynch R, Nakasone E, Schweizer M, Tachiki L, Vinayak S, Wagner M, Yeh A, Huynh-Le M, Rosenstein L, Yu P, Clement J, Daher A, Dailey M, Elias R, Jayaraj A, Hsu E, Menendez A, Rathmann J, Gadgeel S, Hershman D, Accordino M, Bhutani D, Schwartz G, Reuben D, Mushtaq S, Bernicker E, Deeken J, Shafer D, Lewis M, Rhodes T, Gill D, Low C, Mashru S, Mansoor A, Zaren H, Smith S, Nagaraj G, Akhtari M, Lau E, Reeves M, Berg S, Elms D, Morgans A, Wehbe F, Altman J, Gurley M, Mulcahy M, Durbin E, Kulkarni A, Nelson H, Shah S, Rosovsky R, Reynolds K, Bardia A, Boland G, Gainor J, Zubiri L, Halfdanarson T, Bekaii-Saab T, Desai A, Xie Z, Mesa R, Bonnen M, Mahadevan D, Ramirez A, Salazar M, Shah P, Faller B, McKay R, Ajmera A, Cabal A, Shaya J, Weissmann L, Jani C, Knoble J, Glace M, Rink C, Stauffer K, Zacks R, Joshi M, Menon H, Rovito M, Griffiths E, Elshoury A, Jabbour S, Shah M, Bashir B, McNair C, Mahmood S, Mico V, Miller C, Rivera A, Flora D, Logan B, Kloecker G, Mandapakala C, Shah S, Cabebe E, Glover M, Jha A, Schapira L, Wu J, Subbiah S, Revankar S, Stover D, Addison D, Chen J, Gatti-Mays M, Jhawar S, Karivedu V, Lustberg M, Palmer J, Pillainayagam C, Wall S, Williams N, Wulff-Burchfield E, Kasi A, Edwin N, Smits M, Owenby S, Doroshow D, Galsky M, Wotman M, Zhu H, Fazio A, Riess J, Patel K, Rubinstein S, Wood W, Islam J, Kumar V, Ahmad S, Grover P, Gulati S, Kharofa J, Marcum M, Bowles D, Geiger C, Markham M, Bishnoi R, Russ A, Shah C, Acoba J, Rho Y, Feldman L, Hoskins K, Gantt G, Khan M, Pasquinelli M, Schwartz C, Vikas P, Friese C, Mavromatis B, Bijjula R, Zaman Q, Cheng A, Davis E, Duda S, Enriquez K, Gillaspie E, Hausrath D, Hsu C, Johnson D, Li X, Rini B, Slosky D, Shyr Y, Solorzano C, Sun T, Tucker M, Vega-Luna K, Wang L, Puc M, Carducci T, Goldsmith K, Van Loon S, Topaloglu U, Alimohamed S, Rice R, Cabalona W, Pilar C, Peddi P, Rosen L, McCollough B, Hafez N, Herbst R, LoRusso P, Masters T, Stratton C, Koshkin V, Kwon D, Peters S. Racial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer. JAMA Network Open 2022, 5: e224304. PMID: 35344045, PMCID: PMC8961318, DOI: 10.1001/jamanetworkopen.2022.4304.Peer-Reviewed Original ResearchConceptsBlack patientsWhite patientsCOVID-19 outcomesElectronic health recordsCOVID-19Intensive care unit admissionNon-Hispanic white patientsWorse COVID-19 severityWorse COVID-19 outcomesNon-Hispanic Black individualsRacial disparitiesCare unit admissionRetrospective cohort studyCOVID-19 presentationUnique clinical courseCOVID-19 severityPatients' electronic health recordsCOVID-19 diagnosisCause deathUnit admissionClinical characteristicsCohort studyClinical courseMechanical ventilationClinical complicationsAssessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States
Hawley J, Sun T, Chism D, Duma N, Fu J, Gatson N, Mishra S, Nguyen R, Reid S, Serrano O, Singh S, Venepalli N, Bakouny Z, Bashir B, Bilen M, Caimi P, Choueiri T, Dawsey S, Fecher L, Flora D, Friese C, Glover M, Gonzalez C, Goyal S, Halfdanarson T, Hershman D, Khan H, Labaki C, Lewis M, McKay R, Messing I, Pennell N, Puc M, Ravindranathan D, Rhodes T, Rivera A, Roller J, Schwartz G, Shah S, Shaya J, Streckfuss M, Thompson M, Wulff-Burchfield E, Xie Z, Yu P, Warner J, Shah D, French B, Hwang C, Halmos B, Verma A, Gartrell B, Goel S, Ohri N, Sica R, Thakkar A, Stockerl-Goldstein K, Butt O, Campian J, Fiala M, Henderson J, Monahan R, Zhou A, Thompson M, Bohachek P, Mundt D, Streckfuss M, Tadesse E, Lammers P, Panagiotou O, Egan P, Farmakiotis D, Khan H, Olszewski A, Loaiza-Bonilla A, Del Prete S, Bar M, Gulati A, Steve Lo K, Rose S, Stratton J, Weinstein P, Caimi P, Barnholtz-Sloan J, Garcia J, Nakayama J, Gupta S, Pennell N, Ahluwalia M, Dawsey S, Lemmon C, Nizam A, Hoppenot C, Li A, Choueiri T, Bakouny Z, Bouchard G, Busser F, Connors J, Curran C, Demetri G, Giordano A, Kelleher K, Nohria A, Schmidt A, Shaw G, Van Allen E, Nuzzo P, Xu V, Zon R, Zhang T, Halabi S, Leighton J, Lyman G, Graber J, Grivas P, Khaki A, Loggers E, Lynch R, Nakasone E, Schweizer M, Tachiki L, Vinayak S, Wagner M, Yeh A, Gatson N, Goyal S, Huynh-Le M, Rosenstein L, Yu P, Clement J, Daher A, Dailey M, Elias R, Jayaraj A, Hsu E, Menendez A, Rathmann J, Serrano O, Hwang C, Gadgeel S, Singh S, Hawley J, Hershman D, Accordino M, Bhutani D, Schwartz G, Reuben D, Alexander M, Mushtaq S, Bernicker E, Deeken J, Shafer D, Lewis M, Rhodes T, Gill D, Low C, Mashru S, Mansoor A, Zaren H, Smith S, Nagaraj G, Akhtari M, Lau E, Reeves M, Berg S, Elms D, Morgans A, Wehbe F, Altman J, Gurley M, Mulcahy M, Durbin E, Kulkarni A, Nelson H, Sachs Z, Shah S, Rosovsky R, Reynolds K, Bardia A, Boland G, Gainor J, Zubiri L, Halfdanarson T, Bekaii-Saab T, Desai A, Xie Z, Mesa R, Bonnen M, Mahadevan D, Ramirez A, Salazar M, Shah D, Shah P, Faller B, McKay R, Ajmera A, Brouha S, Cabal A, Hsiao A, Kligerman S, Shaya J, Weissmann L, Jani C, Thomson C, Knoble J, Glace M, Rink C, Stauffer K, Zacks R, Blau S, Joshi M, Menon H, Rovito M, Griffiths E, Elshoury A, Jabbour S, Misdary C, Shah M, Bashir B, McNair C, Mahmood S, Mico V, Rivera A, Flora D, Logan B, Kloecker G, Mandapakala C, Shah S, Cabebe E, Glover M, Jha A, Schapira L, Wu J, Subbiah S, Lopes G, Revankar S, Stover D, Addison D, Chen J, Gatti-Mays M, Jhawar S, Karivedu V, Lustberg M, Palmer J, Wall S, Williams N, Wulff-Burchfield E, Kasi A, Edwin N, Smits M, Chism D, Owenby S, Doroshow D, Galsky M, Wotman M, Zhu H, Fu J, Fazio A, Sueyoshi M, Huber K, Riess J, Patel K, Rubinstein S, Wood W, Jensen C, Kumar V, Wise-Draper T, Ahmad S, Grover P, Gulati S, Kharofa J, Latif T, Marcum M, Park C, Shaikh H, Bowles D, Geiger C, Markham M, Bishnoi R, Russ A, Shah C, Acoba J, Rho Y, Feldman L, Hoskins K, Gantt G, Liu L, Khan M, Nguyen R, Pasquinelli M, Schwartz C, Venepalli N, Vikas P, Friese C, Fecher L, Mavromatis B, Bijjula R, Zaman Q, Warner J, Cheng A, Davis E, Duda S, Enriquez K, French B, Gillaspie E, Hennessy C, Hausrath D, Hsu C, Johnson D, Li X, Mishra S, Reid S, Rini B, Slosky D, Shyr Y, Solorzano C, Sun T, Tucker M, Vega-Luna K, Wang L, Kennecke H, Aboulafia D, Schroeder B, Puc M, Carducci T, Goldsmith K, Van Loon S, Topaloglu U, Alimohamed S, Rice R, Cabalona W, Pilar C, Peddi P, Rosen L, McCollough B, Bilen M, Ravindranathan D, Hafez N, Herbst R, LoRusso P, Masters T, Stratton C. Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States. JAMA Network Open 2022, 5: e2142046. PMID: 34982158, PMCID: PMC8728628, DOI: 10.1001/jamanetworkopen.2021.42046.Peer-Reviewed Original ResearchMeSH KeywordsAgedCause of DeathCensusesCOVID-19FemaleHealth FacilitiesHumansIntensive Care UnitsMaleMiddle AgedNeoplasmsOdds RatioPandemicsRegistriesRespiration, ArtificialRetrospective StudiesRisk FactorsRural PopulationSARS-CoV-2Severity of Illness IndexSocial VulnerabilitySpatial AnalysisUnited StatesUrban PopulationConceptsCOVID-19 outcomesRural-Urban Continuum CodesCohort studyLaboratory-confirmed SARS-CoV-2 infectionMortality rateUS census divisionsRegistry-based retrospective cohort studyIntensive care unit admissionRegistry-based cohort studySARS-CoV-2 infectionPatient-level risk factorsSecondary composite outcomeCare unit admissionRetrospective cohort studyCare of patientsCensus divisionsInvasive malignant neoplasmCOVID-19Significant differencesCOVID-19 diagnosisCause deathUnit admissionCause mortalityComposite outcomePatient characteristics
2021
Clinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection
McPadden J, Warner F, Young HP, Hurley NC, Pulk RA, Singh A, Durant TJS, Gong G, Desai N, Haimovich A, Taylor RA, Gunel M, Dela Cruz CS, Farhadian SF, Siner J, Villanueva M, Churchwell K, Hsiao A, Torre CJ, Velazquez EJ, Herbst RS, Iwasaki A, Ko AI, Mortazavi BJ, Krumholz HM, Schulz WL. Clinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection. PLOS ONE 2021, 16: e0243291. PMID: 33788846, PMCID: PMC8011821, DOI: 10.1371/journal.pone.0243291.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionYale New Haven HealthSARS-CoV-2Hospital mortalityRisk of admissionMale sexRisk factorsSARS-CoV-2 testingInvasive mechanical ventilationSevere acute respiratory syndrome virusBurden of diseaseRT-PCR testingAcademic health systemDiverse patient populationsRespiratory syndrome virusEthnic groupsAdult patientsClinical characteristicsDischarge dispositionRespiratory supportPrimary outcomeTreatment guidelinesMechanical ventilationRetrospective studyPatient population
2020
Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non–small-cell lung carcinoma
Boulle G, Velut Y, Mansuet-Lupo A, Gibault L, Blons H, Fournel L, Boni A, Cremer I, Wislez M, Duchatelle V, Trédaniel J, Hammond S, Herbst R, Alifano M, Giraud P, Damotte D. Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non–small-cell lung carcinoma. European Journal Of Cancer 2020, 135: 221-229. PMID: 32610210, DOI: 10.1016/j.ejca.2020.04.040.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesChemoradiotherapyChemoradiotherapy, AdjuvantFemaleForkhead Transcription FactorsHumansLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm StagingRetrospective StudiesTime FactorsTreatment OutcomeTumor MicroenvironmentConceptsT-cell densityCell lung carcinomaN2 NSCLCPatient survivalLung carcinomaClinical dataT cellsRadiotherapy efficacyIII-N2 NSCLCSurgery/chemotherapyPD-L1 expressionStandard of careImmunogenic cell deathDouble-positive cellsAction of radiotherapyIII-N2Immune environmentAbscopal effectChemoradiotherapy efficacyImmune infiltrationImmune cellsPositive cellsMultivariate analysisRadiotherapyTumor samplesImmune 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 outcomesExpression 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 analysisEGFR 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 levelsDisparities in broad-based genomic sequencing for patients with advanced non-small cell lung cancer
Riaz F, Presley CJ, Chiang AC, Longtine JA, Soulos PR, Adelson KB, Herbst RS, Nussbaum NC, Sorg RA, Abernethy AP, Agarwala V, Gross CP. Disparities in broad-based genomic sequencing for patients with advanced non-small cell lung cancer. Journal Of Geriatric Oncology 2019, 10: 669-672. PMID: 30718180, DOI: 10.1016/j.jgo.2019.01.016.Peer-Reviewed Original Research
2018
Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting
Presley CJ, Tang D, Soulos PR, Chiang AC, Longtine JA, Adelson KB, Herbst RS, Zhu W, Nussbaum NC, Sorg RA, Agarwala V, Abernethy AP, Gross CP. Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting. JAMA 2018, 320: 469-477. PMID: 30088010, PMCID: PMC6142984, DOI: 10.1001/jama.2018.9824.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDNA, NeoplasmFemaleGenes, erbB-1GenomicsGenotypeHumansImmunotherapyLung NeoplasmsMaleMiddle AgedMutationNeoplasm StagingReceptor Protein-Tyrosine KinasesRetrospective StudiesSequence Analysis, DNASurvival AnalysisConceptsAdvanced non-small cell lung cancerNon-small cell lung cancerCommunity oncology settingCell lung cancerLung cancerOncology settingRoutine testingNonsquamous non-small cell lung cancerTargeted treatmentPropensity score-matched survival analysisStage IIIB/IVFlatiron Health databaseIIIB/IVRetrospective cohort studyThird-line treatmentFirst-line treatmentMinority of patientsUnadjusted mortality ratesEGFR/ALKCohort studyOverall survivalSecondary outcomesUnmatched cohortPrimary outcomeAntineoplastic treatmentSpatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer
Villarroel-Espindola F, Yu X, Datar I, Mani N, Sanmamed M, Velcheti V, Syrigos K, Toki M, Zhao H, Chen L, Herbst RS, Schalper KA. Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer. Clinical Cancer Research 2018, 24: 1562-1573. PMID: 29203588, PMCID: PMC5884702, DOI: 10.1158/1078-0432.ccr-17-2542.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntigens, CDAntigens, Differentiation, MyelomonocyticB7 AntigensB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesEvaluation Studies as TopicFemaleGene Expression Regulation, NeoplasticHumansImmunologic FactorsImmunotherapyLung NeoplasmsMaleMembrane ProteinsMutationProgrammed Cell Death 1 ReceptorRetrospective StudiesConceptsNon-small cell lung cancerHuman non-small cell lung cancerT helper cellsCytotoxic T cellsT cellsPD-1Localized expression patternQuantitative immunofluorescenceTumor-infiltrating lymphocytesCell lung cancerLung cancer casesGenomic analysisTissue microarray formatTumor-associated macrophagesPD-L1 proteinCytoplasmic staining patternClin Cancer ResExpression patternsLow mutational burdenTumor epithelial cellsSpecific genomic alterationsVISTA expressionVISTA proteinPD-L1Immunomodulatory role
2017
Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery
Salazar MC, Rosen JE, Wang Z, Arnold BN, Thomas DC, Herbst RS, Kim AW, Detterbeck FC, Blasberg JD, Boffa DJ. Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery. JAMA Oncology 2017, 3: 610-619. PMID: 28056112, PMCID: PMC5824207, DOI: 10.1001/jamaoncol.2016.5829.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungChemotherapy, AdjuvantDrug Administration ScheduleFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm GradingNeoplasm StagingPneumonectomyPostoperative PeriodProportional Hazards ModelsRetrospective StudiesTreatment OutcomeUnited StatesConceptsLung cancer surgeryCell lung cancer resectionAdjuvant chemotherapyLung cancer resectionNational Cancer DatabaseCell lung cancerLower mortality riskCancer surgeryCox modelCancer resectionLung cancerCancer DatabaseMortality riskCell lung cancer surgeryHospital-based tumor registryIncident lung cancer casesPostoperative multiagent chemotherapyInitiation of chemotherapyTreatment-naive patientsPropensity-matched pairsRetrospective observational studyLymph node metastasisLung cancer casesChemotherapy initiationPostoperative chemotherapy
2016
Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer. JAMA Oncology 2016, 2: 1-9. PMID: 26562159, PMCID: PMC4941982, DOI: 10.1001/jamaoncol.2015.3638.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibody SpecificityB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLung NeoplasmsMaleObserver VariationPredictive Value of TestsReproducibility of ResultsRetrospective StudiesTissue Array AnalysisConceptsTumor-infiltrating lymphocytesPD-L1 expressionPD-L1 antibodiesPD-L1 protein expressionCell lung cancerPD-L1Whole tissue sectionsQuantitative immunofluorescenceLung cancerChromogenic immunohistochemistryPoor concordanceDifferent PD-L1 antibodiesHigh tumor-infiltrating lymphocytesTumor PD-L1 expressionPD-L1 protein levelsCell lung cancer biopsiesMonoclonal antibodiesCurrent consensus guidelinesProtein expressionDurable clinical responsesMain outcome measuresEarly phase trialsLung cancer biopsiesRabbit monoclonal antibodyCorresponding tissue microarrays
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 analysisObjective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer
Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, Herbst RS, Rimm DL. Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer. Journal Of The National Cancer Institute 2015, 107: dju435. PMID: 25650315, PMCID: PMC4565530, DOI: 10.1093/jnci/dju435.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD20Carcinoma, Non-Small-Cell LungCD3 ComplexCD8 AntigensConfounding Factors, EpidemiologicFluorescent DyesHumansIndolesKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMicroscopy, FluorescencePredictive Value of TestsRetrospective StudiesT-Lymphocytes, CytotoxicConceptsTumor-infiltrating lymphocytesLevels of CD3TIL subtypesMultivariable analysisTumor sizeLonger survivalAssociation of TILsLevel of TILsNon-small cell lung cancerNon-small cell lung cancer samplesLocal immune effectsClinico-pathologic characteristicsImmune checkpoint inhibitorsCell lung cancerCell lung cancer samplesLung cancer samplesDifferent tumor compartmentsObjective measurementsElevated CD3High CD20TIL markersTIL subpopulationsCheckpoint inhibitorsSmoking historyHistology type