N2 Disease in T1 NonSmall Cell Lung Cancer文档格式.docx

N2 Disease in T1 NonSmall Cell Lung Cancer文档格式.docx

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Email:

wigle.dennis@mayo.edu

Thepublisher'

sfinaleditedversionofthisarticleisavailableatAnnThoracSurg

Seecommentary"

SonicHedgehog（SHH）PromotestheDifferentiationofMouseCochlearNeuralProgenitorsviatheMath1–Brn3.1Signalingpathwayinvitro"

inJNeurosciRes,volume88on 

page 

928.

∙ 

OtherSections▼

oAbstract

oMaterialandMethods

oResults

oComment

oReferences

Abstract

Background

Theoptimalmanagementstrategyformediastinalstaginginearly-stagenon-smallcelllungcancer（NSCLC）isnotclearlydefined.Thetrueprevalenceofmediastinallymphnodemetastases（N2disease）inresectedpathologicT1（pT1）NSCLCmustbeknowntodefinetheroleofinvasivemediastinalstaginginthesepatients.

Methods

DataofpatientswithpT1lesionsresectedatMayoClinicbetween1998and2006wereretrospectivelyreviewed.PatientswithN2diseasewereidentifiedfrompathologyandoperativereports.Werevieweddemographics,radiologicdata,andsurgicalproceduresforthosewithpathologicT1N2NSCLC.

Results

Weidentified968casesofpT1lesions,59withpN2disease（6.1%）.ForthosewithT1N2disease,theprimarylunglesionwasperipheralin18（31%）andcentralin41（69%）.Ofthese,36hadnegativenon-invasivemediastinalstaging（3.7%）andwereincidentallydiscovered.Themostfrequentlyaffectedlymphnodestationwas7in22patients（37%）,followedby5,6in18（31%）.Mediastinoscopyfoundpositivelymphnodesin3of16patients（19%）inwhichitwasperformed.Overall5-yearsurvivalforpT1N2incidentallydiscoveredduringmediastinallymphnodedissectionatthetimeoflungresectionwas46%（95%confidenceinterval,31%to68%）.

Conclusions

TruepT1NSCLCharborsarelativelylowrateofN2disease.TherateofoccultN2diseasenotobservedonnoninvasivepreoperativemediastinalstagingisevenlower.ForpatientswithT1NSCLCandnegativemediastinalimaging,routinemediastinoscopyresultsinalowyieldofoccultN2diseasediscovery.

CurrenttreatmentalgorithmsforlocallyadvancedstageIIInon-smallcelllungcancer（NSCLC）typicallyinvolveneoadjuvantordefinitivechemoradiationtherapy.SurgicalresectionisnotnormallyusedasinitialtreatmentinmostNorthAmericancenters.Asaconsequence,mucheffortisdirectedtowardtheassessmentofmediastinallymphnodesformetastaticdiseasebeforeanyplannedsurgicalresection.

Computedtomography（CT）hasasensitivityof50%to76%andspecificityof55%to86%forpredictingmeta-staticinvolvementofmediastinallymphnodeswhentheyexceed1cmintheshortaxis[1–3].Positronemissiontomography（PET）hasemergedasausefultooltoevaluatethemediastinum,withasensitivityof83%to91%andspecificityof70%to91%forlymphnodemetastases[3,4].Despitethesenumbers,pathologictissueconfirmationisdesirabletoprovethatalesionisindeedmalignantandnotexcludepotentiallyresectabletumorsfromsurgicaltreatmentandpotentialcure.

SomehavesuggestedthattheincidenceoflymphnodemetastasesinpatientswithclinicalT1NSCLCandnegativenoninvasivemediastinalstagingmightbelowenoughtoprecluderoutineinvasivestagingbymediastinoscopy[5,6].ReportsvaryaboutthetruerateofoccultN2diseaseinNSCLCpatientswithnegativenoninvasivestaging,particularlyforpatientswithT1lesions.TheobjectiveofthisstudywastodescribetheincidenceofN2diseasein968consecutivecasesofresectedpathologicT1（pT1）NSCLCandmakeinferencesabouttheutilityofinvasivemediastinalstaginginthissubgroupofpatients.

MaterialandMethods

ThisstudywasapprovedbytheMayoClinicCollegeofMedicine’sInstitutionalReviewBoard.

Patients

WereviewedourprospectivedatabaseforallpatientsthatunderwentresectionforpT1NSCLCbetween1998and2006atMayoClinic,Rochester,Minnesota.Allpathologyreportsforthesepatientswerereviewed.Weidentified968casesinvolvingsurgicalproceduresinpatientswithpT1NSCLC.Ofthese,59（6.1%）werefoundtohavepathologicN2（pN2）disease.Preoperativedatawerereviewedforthisgroup,includingage,gender,pulmonaryfunctiontests,localizationoftheprimarytumor,presenceofadenopathyonCTscan,andsizeandmetabolicactivityonPETscaninthosepatientsforwhichitwasperformed.Thesurgicalandpathologyreportswerereviewedforthemediastinallymphnodesstationsthatweresampledandwhichofthemcontainedmetastases.

LesionswerestagedaccordingtothestagingsystemandmediastinallymphnodemapdescribedbyMountain[7,8].Thesizeofthelesionwasdeterminedfromthegreatestdimensionmeasuredinthepathologylaboratory.

ImagingData

AlltheavailableCTscanswerereviewed.PeripherallungnodulesweredefinedonCTscanastumorswiththecenterlocatedintheouterthirdofthelungineitherthesagittalorcoronalplane.IfCTimageswerenotavailable,aperipherallesionwasdefinedaccordingtoitsrelationtothepleuralsurfaceasdescribedinthepathologyreport.MediastinallymphnodeswereconsideredtobepositivebyCTscancriteriawhentheirshortaxiswas10mmormoreinsize.InpatientsinwhomPETscanswereperformed,reportswerereviewedandconsideredpositiveifthedescribedmetabolicactivityinthemediastinumexceeded1.5-foldoverbackgroundlevels.

Mediastinoscopy

Cervicalmediastinoscopywasperformedinthestandardfashionandselectively,determinedbythepresenceofsignificantlymphnodesinthemediastinumobservedonCTscan,byincreasedmetabolicactivityonPET,orbysurgeonpreference.Afterintroductionofthemediastinoscope,biopsyspecimensfromstation4R,7,and4Lweretypicallyobtained.Biopsyspecimenswerealsoobtainedfromotherstationswhenlymphnodeswereencounteredorspecificallysoughtout.

MediastinalLymphNodeDissection

Mediastinallymphnodedissection（MLND）wasperformedaspartoflungresections.Forright-sidedprocedures,thelymphnodestations2R,4R,7,and9wereroutinelydissected;

forleft-sidedprocedures,thenodesfromstations5,6,7,and9wereincluded.Onbothsides,otherlymphnodestationsencounteredorspecificallysoughtoutatthetimeofthelungresectionwerealsoremoved.

Statistics

Descriptivestatisticsarereportedasmedianandrangeforcontinuousvariablesandasfrequencyandpercentagefordiscretevariables,basedontumorstatus（N2vsN0/N1）.AssociationswithtumorstatusweremadeusingtheWilcoxonranksumtestforcontinuousvariablesandχ2testorFisherexacttestasappropriatefordiscretevariables.Theα-levelwassetat0.05forstatisticalsignificance.

Between1998and2006,968patientsunderwentlungresectionforpT1NSCLC.Ofthese,59（6.1%）werefoundtohaveN2disease（32men,27women）.Peripherallesionswerefoundin18patientsandcentrallesionsin41（69%）.Lungtumorswereontherightsidein25（43%）andontheleftsidein34（57%）.Lobectomybyopenthoracotomywasperformedin54（92%）,andwedgeresectionin5（8%）.PatientcharacteristicsarelistedinTable1.

Table1

CharacteristicsforpT1N2Patients

CTcriteriawereusedtoestablishmediastinaladenopathyin17of59patients（29%）.ThemostfrequentlymphnodestationfoundtobepositivebyCTscancriteriawasstation4Rin10patients（17%）,followedbystation7in6（10%）.In8patients（14%）,CTshowedadenopathyinN1-levellymphnodes.

PETscanwasdonein27patients（46%）,resultingin18（31%）withnegativemediastinallymphnodesand9（15%）withpositivenodes.In3patientstheCTandPETscanswerebothpositiveforthesamelymphnodestations.In2patientsthisinvolvedstation4Rwithmetastasesfoundattimeofoperationafteranegativemediastinoscopy.Theremainingcaseinvolveda5,6lymphnodestation,withmetastasisconfirmedduringleft-sidedlungresection.

SurgicalData

Mediastinoscopywasperformedin16of59T1N2patients（27%）,andin11of23withpreoperativefeaturesofN2disease.In3of16patients（19%）,mediastinoscopyfoundlymphnodemetastasesinthemediastinum,and2subsequentlyreceivedneoadjuvantchemoradiationtherapy,followedbypulmonaryresection.Thethirdpatienthadcomplicationswithbleedingduringthemediastinoscopyprocedure,forwhichathoracotomywasperformedalongwiththelungresection.Intheremaining13patients（81%）,mediastinoscopydidnotrevealthepresenceoflymphnodemetastases,despitethediscoveryofN2diseaseduringMLNDatthetimeoflungresection.Overall,mediastinoscopywasabletoidentifymediastinallymphnodeinvolvementinonly3of9patients（33%）wherethepositivelymphnodeswerewithinthefieldaccessiblebycervicalmediastinoscopy.

InN2-positivecases,themediansizeoftheT1pulmonarylesionswas2cm（range,0.9to3cm）.Only1lesionwaslessthan1cm,37lesionsmeasuredbetween1and2cm,and21lesionsweremorethan2cminthegreatestdimension.ThelocationoftheprimarylesionforspecificN2-positivestationsisdescribedinTable2.

Table2

Fr