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.
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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