Post on 01-Apr-2020
MalignantLesionsoftheLarynx
ReneePennM.D.
Head&NeckOncologyFellowDivisionofHeadandNeckSurgeryUniversityofCalifornia,LosAngeles
Incidence• 10KnewcasesoflaryngealcancerinU.S.annually
– 3,900deathsannually
• Gender– Since1950‐M:Fratio15:15:1in2004 – womenhaveequalplaceinthetoxicworkenvironment– cigarettesmoking
• Riskfactors:– Tobacco
• 13‐foldriskforlaryngealcancerforsmokers• riskincreaseswithincreasingtobaccouse
– Alcohol• 34‐foldriskforlaryngealcancerifconsume>1.5Lwine/day
– Teatime?• mateinLatinAmericaandchimarrainBrazil
DecreasingSurvivalAmongPa<entswithLaryngealCancer
• NCDBanalysis:• mid‐1980stomid‐1990s.
• Increasedchemo‐radiation,decreasedopensurgery,increasedendoscopicresection
• Themostnotabledeclineinthe5‐yearrelativesurvival:• advanced‐stageglotticcancer• early‐stagesupraglotticcancers
• “Thedecreasedsurvivalrecordedforpatientswithlaryngealcancerinthemid1990smayberelatedtochangesinpatternsofmanagement.”
Hoffman et al. Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival. Laryngoscope. 2006 Sep;116(9 Pt 2 Suppl 111):1-13.
Gene<cs/Riskfactors
Aneuploidy
Tumorsuppressorgeneinactivation Genelocus17p13:mutantp53………………………….DNArepair,apoptosis Genelocus9p21:mutantp16………………………….Cellcycleregulation
Proto‐oncogeneactivation Proto‐oncogene(11q13)ampli`iescyclinD1……….Cellcycleregulation
Mutagen‐inducedchromosomebreaks
HPV Types16and18:E6andE7viralprotein‐mediateddegradationofp53 Oropharyngealmalignancy
GERD Koufman:n=31withglotticSCC,GERDdocumentedin84%;only58%weresmokers
Embryology
• Frazer(1909)– supraglottisoriginatesfromthebuccopharyngealprimordium
• highriskofbilateralneckdiseasevs.glottictumors‐metastasizeipsilaterally
• Pressman(1956)– separatederivationfromglottis‐supraglottictumorsofsubstantialbulkdonotspreadacrossthelaryngealventricletothevocalcord
• TuckerandSmith(1982)– Dyestudiesanatomicallybasedcon`irmationre:elastictissuebarriers
• Formedbasisofpartiallaryngealsurgery• AlreadyadvocatedbyBiller
Cummings:otolaryngology,4thed‐2005‐Mosby,Inc.
Anatomy• Fibroelasticmembranes
– Barrierstocarcinomaspread• Quadrangularmembrane
– Superiorfreeedge=AEfold– Inferiorfreeedge=Falsecord
• Conuselasticus– Supportsvocalfold– Lateralattachmentatcricoid– Medialattachmentatanteriorthyroidcartilage
– Freeedgeformsvocalligament
Cummings:otolaryngology,4thed‐2005‐Mosby,Inc.
Pre‐epigloNcspace&Para‐gloNcspace
• Pre‐epiglotticspace– Anterior:thyrohyoidmembrane&thyroidcartilage
– Posterior:epiglottiselasticcartilage
– Inferior:Petioleattachmenttothyroidcartilage
• Conduit:– elasticepiglotticcartilagehasperforations‐directextensionofinfrahyoidsupraglotticcancerintothisfascia‐boundspace
• Bilateralneckdrainage
• Paraglotticspace– quadrangularmembraneinferiorly– conuselasticusanteriorlyand
medially– thyroidcartilagelaterally
Myers:Laryngoscope,Volume106(5).May1996.559‐567Cummings:otolaryngology,4thed‐2005‐Mosby,Inc.
TransgloNctumors
• Usuallyinitiateassupraglotticorglotticcancers• McGravan(1961)
– mustcrossthreeregions:falsecords,ventricle,truecord– altersprognosis
• Failthecompartmentalizationhypothesis– directmucosalextension– paraglotticspace
McGavran et al. Cancer 1961.
Diagnosis
• Dysphagia• Vocalchanges• Aspiration• Otalgia• Blood‐tingedsputum• Neckmass• Cachexia• Dyspnea• Pain• Halitosis
NaturalHistoryWITHOUTTreatment
• Hemoptysis>supraglottictumors• Dysphonia>TVC/glotticlesions• AirwayObstruction>insidioussubglottictumors• Aspiration>supraglottic(alsowithincompetentglottis)• Otalgia>supraglottic(in`iltrationofmusculature)• Dysphagia:anylocation,muscle,sensory,motor,joint
Histology• >95%SCC
– Variations:• verrucouscarcinoma,spindlecellcarcinoma,basaloidSCC,andpapillarySCC
• Othertypesofcarcinoma:– neuroendocrinecarcinoma– lymphepitheliomatouscarcinoma– adenocarcinoma– others(sarcomas,lymphomas)– adenoidcystic(tracheamorethansubglottis)
• Underlying:– hyperplasia,dysplasia,CIS
• Overlying:– surfacekeratinizationmaybepresent.
Histology
• Mucosa:5‐7celllayers– strati`iedsquamousepithelium,(eg,ventricle,falsecord,andsubglottis)
• Mitotic`igures:– presentinthebasallayer– shouldbeabsentabovethissecondlayer
• CIS:full‐thicknessatypiaofthesquamouscells
• Atypiaischaracterizedbythecellarchitecture:– mitosescountperhpf,highNCratio,largenucleoli
• Differentiationischaracterizesbythetissuearchitecture:– well,moderately,orpoorlydifferentiated
Whatchagot???
• Patientswithglottictumorsareseenearlybecauseofhoarseness….– Biopsy!!!!!
• Oops!– fungallaryngitis,sarcoidosis,tuberculosis,orWegener'sgranulomatosis,pseudoepitheliomatoushyperplasia(granularcellmyoblastoma)
• The`ivecategoriesoflaryngealsquamouscellabnormality(frombenigntoclearlymalignant):– hyperkeratosis– hyperkeratosiswithatypia– carcinomainsitu(CIS)– super`iciallyinvasivecarcinoma– invasivecarcinoma
H,H+A,CIS
• hyperkeratosis+/‐atypiaandCIS– conservativemanagement:strippingofVC– 5%–30%withfutureinvasivecancer
• follow‐upandpossiblere‐biopsy6‐12weeks
Superficiallyinvasivevs.InvasiveSCC
Whycare?
Cummings:otolaryngology,4thed‐2005‐Mosby,Inc.
Superficialvs.InvasiveGloNcSCC
• Super`icialinvasivecarcinomavs.CIS– ItisallabouttheSLP!!!!!
• “Thecentralthird”– earlysymptomsofvoicechange
• Samplingerror:– Slaughter'shypothesisof`ieldcancerizationasdescribedoriginallyfortheoralcavity(1946)
Managementofprecancerouslesions
• Radiotherapy…notsomuch!!!– failure(10%)– nofutureoptionforXRTT1/T2
• Surgery– Generousstripping– Informedconsentre:multipletreatments– Goodcompliance(years)– Supravitalstainingwithtoluidineblue– Rapidorfrequentrecurrence
• Smokingcessationprogrammustbepartofmanagement!!!!
Peepsyouknow…thingsyoushouldknow…• BlackwellKE,CalcaterraTC,FuYS.Laryngealdysplasia:epidemiologyand
treatmentoutcome.AnnOtolRhinolLaryngol.1995Aug;104(8):596‐602.
• Retrospective(n=65)long‐termfollow‐upforlaryngealsquamousdysplasia
• Results:– 33patientsdemonstratingmoderatedysplasia,severedysplasia,orcarcinomainsitu– Invasivecarcinomadevelopedin…
• 10of21patients(48%)treatedendoscopicallyallsalvaged!!!!!• 0of12patientstreatedbymoreaggressiveTx(EBRT,partiallaryngectomy,orTL)
– Laryngealpreservation• 15of21patients(71%)intheendoscopictreatmentgroup• 11of12patients(92%)intheaggressivetreatmentgroup……..(notstatisticallysigni`icant)
• “Weconcludethatthereisamoderatelyhighrateofprogressiontoinvasivecarcinoma….However,withclose,longtermfollowup,patientsundergoingendoscopictherapyhaveanoveralloutcomesimilartothatinpatientstreatedwithpartiallaryngectomyorradiotherapypriortodevelopinginvasivedisease.”
Radiology
• Tumorextent(limitationsofendoscopy)– Pre‐epiglotticspaceandparaglotticspaceinvolvement,cartilageerosion
• MRI:– high‐densitytumorvsfatinthepreepiglotticspace– Softtissueinvasion– Nodaldisease
• ECS
• CT:thyroidcartilagedestruction– (presencemandatesatotallaryngectomy)– Stillundercallscartilageinvasion
EarlyGloNcCancer(T1/T2)• Lessbiologicallyaggressivethansupraglotticorhypopharyngeal
– welltomoderatelydifferentiated– remainslocalizedtotheglotticcompartmentlonger– withoutneckordistantmetastases:sparsesubmucosallymphatics
• Symptomspresentearly– mosttumorsoriginateonthefreesurfaceofthetruevocalfold– anteriortwo‐thirds‐hoarsenessinvitesmedicalevaluation
• Treatment– radiotherapyorconservationsurgery– noneedforelectiveND– surgeryoffers90%to95%cureratesforT1lesions*****– surgicalsalvagetotallaryngectomy
• equallong‐termcurebutwithdifferentmorbidities
***superstarstatusmaterial
EarlyGloNcCancer:Effectofanatomyonmanagement
• Radiationfailuresite:– Sub‐glottis,anteriorcommissure,andarytenoidinvolvement
• Middlethirdlesions– Easiesttocure:
• respondwelltoXRT,endoscopic‐laserresection,oropencordectomy– Cureratesapproach100%;95%curerateforradiotherapy
• Anteriorcommissure– ConcernsregardingXRT:mixedreportsforT1lesions– Cure‐50‐92%
Hemi‐laryngectomyaberXRTFailure
• Billeretal1970:– LesionlimitedtooneVC
• mayinvolvetheanteriorcommissure,butnotcontralateralVC– Bodyofarytenoidfreeoftumor– Sub‐glotticextension<5mm– MobileVC– Nocartilageinvasion– Recurrencecorrelatingwithinitialtumor
Sub‐gloNcSCC
• 1%oflarynxcancers
• Clinicalpresentation:– airwayobstruction– noresponsetomanagementforCOPD– airwayinsuf`iciency&immediatereliefwhenintubated
• Belowconuselasticus(1cmbelowfreeedgeoftheTVC)– Localspread:
– cricoidcartilageandthyroidgland– Lymphaticspread:
– LevelIVnodes,Delphiannode,andparatrachealnodes
ManagementofSubgloNcSCC
• MandatesTL– laryngealframeworkinvasionisfrequent
• Adjunctprocedures:1. Ipsilateralthyroidectomy2. paratrachealND
• AdjuvantXRT– positivenodes– extensiveinvasion– portsmustincludethesuperiormediastinum
• Monitorforstomalrecurrence
…Badjuju…
• VChypomobility– reducesthecurerates– advantageofsurgeryoverradiation
• Arytenoidinvasion– Highriskforpost‐opdysphagiainorgan‐sparingprocedures
WhatOurVeteransHaveTaughtUs
• DepartmentofVeteransAffairs(VA)LaryngealCancerStudy– NEJM,1991– Randomassignment:StageIII&IVlaryngealSCC
• TLandadjuvantXRT• InductionchemoTxwithcisplatinand`luorouracil,followedbyXRT
• (if+responsetoinductionchemotherapy)• SalvageTL
• IfnoresponsetochemoTx• Residual/recurrentdiseaseafterabove2
– Results• 2yearsurvivalratein`irst2groups(non‐salvagegroups)was68%• laryngealpreservation:possiblein64%ofinductionchemotherapy(41%overall)
• “Theef`icacyofchemotherapyfollowedbyradiotherapy(withsurgicalsalvage)wassimilartothatofsurgeryfollowedbyradiotherapyandofferedtheaddedbene`itoflaryngealpreservationintwothirdsofthepatientstreatedbythisapproach.“
RTOG(Radia<onTherapyOncologyGroup)• NEJM,2003• StageIII&IVlaryngealSCC*• Premise:XRTalonesurvivalandlaryngealpreservationsimilarto
thoseachievedintheVAstudy(*ie.Wedon’tneednostinkin’chemo….)– InductionchemoTxfollowedbyXRT– ConcurrentchemoXRt– XRTalone
• *patientswithlarge,T4lesions(tumorsextendingthroughthethyroidcartilageorintothebaseofthetongue)wereexcluded
• Results:– 2and5yearsurvivalratesweresimilaramongthethreegroups– concurrentchemotherapy:higherratesoflaryngealpreservationandlocalcontrol
– acutetoxiceffectswerehigherinbothchemotherapygroupsthanintheXRTgroup
– latetoxiceffects,includingswallowingdysfunction,weresimilarinallthreegroups
RTOG(Radia<onTherapyOncologyGroup)
“Thesedatacon`irmthatinitialtreatmentaimedatlaryngealpreservationisarealisticandfeasibleoptionformostpatientswithintermediate‐orlate‐stagelaryngealcancer.Theoutcomeinpatientsabletotoleratechemotherapywillbebestwithconcurrentchemotherapyandradiotherapy.Theuseofinductionchemotherapyfollowedbyradiotherapyisnotsupportedbytheresultsofthistrial,andpatientsunabletotolerateconcomitantchemotherapyandradiotherapyshouldreceiveradiotherapyalone.”
“Oftencancerseemstohavelimits,whilethesurgeonseemstohavenone…Weshouldmakeeffortstoforceuponourknifethesamelimitsasthosewhichsurroundingtissuesorstructuresforceuponcanceranditsspread.“
…Partiallaryngealsurgery…
Boccaetal.Extendedsupraglotticlaryngectomy.Reviewof84cases.AnnOtolRhinolLaryngol1987;96:384.
Ouch!!!!
SupragloNcSCC
• Amenabletoorgan‐sparingpartiallaryngectomy
• Endoscopic:Earlysupraglottictumors(suprahyoid)– electrocauteryorbycarbondioxidelaser– bestforsuprahyoidlesions:noinvasionofpre‐epiglotticspace
– infrahyoidtumors–notsomuch!
• Whathasn’tchanged…– Cervicalmetastasis– Bilateral
TLM(Transorallasermicrosurgery)• Prospective,multi‐center
• TLMin117patients• T2toT4lesions,stageIIIorstageIV,glotticorsupraglotticSCC• ND(91patients),andadjuvantradiotherapy(45patients)
• Outcomes‐5‐yearestimates:• localcontrol(74%),locoregionalcontrol(68%),disease‐freesurvival(58%),overallsurvival(55%),distantmetastases(14%)
• ...similartoothermodalities…
• QOL?• 2patients(3%)weretracheotomydependent• 4patients(7%)werefeedingtubedependent
Hinnietal.TransoralLaserMicrosurgeryforAdvancedLaryngealCancer.ArchOtolaryngolHeadNeckSurg.2007;133(12):1198‐1204.
Uwitme???“EligibilitycriteriaforTLMarebroad…
Contraindications:inadequateendoscopicaccess,extensionoftumortoinvolvethegreatvesselsoftheneck,markedextensionoftheprimarytumorandthenodaldiseasemergedorencasedaroundthegreatvessels,andtumorextensionwhichwouldputthepatientatriskforaspiration(ie,bilateralarytenoidinvasion)...
UnlikechemoandXRT,selectpatientswithlarge‐volumeT4tumorsareeligibleforTLM…(wouldyoudothistoyourmother??)
Inaddition,norigidage‐related,hematological,biochemical,orperformancestatuscriteriaprecludepatientsfromTLMsurgery.”
Hinnietal.TransoralLaserMicrosurgeryforAdvancedLaryngealCancer.ArchOtolaryngolHeadNeckSurg.2007;133(12):1198‐1204.
Notheydiin’t!!RTOGtrial: Givencomparablesurvivaloutcomesb/wnsurgeryandorgansparingTxthelogicalpreferencemustbeforanonsurgicalorgan‐preservingapproach.
Hinnietal: “Thisviewlargelyignoredtheestablishedroleofcurrent openpartiallaryngectomytechniquesandagrowing expertisewithorgan‐preservingTLMinEuropeandNorth America.Inrespondingtothiscontention….Thedatapresented hereincanspeci`icallycomparetheoutcomesofTLMwith orwithoutadjuvantRTtotheRTOGTrialdata.”
Hinnietal.TransoralLaserMicrosurgeryforAdvancedLaryngealCancer.ArchOtolaryngolHeadNeckSurg.2007;133(12):1198‐1204.
Double‐EdgedSword?OrCan’tGoWrong?
XRTworsethanlaryngealpreservation?….Butbothareorgansparing…..
Conserva<onLaryngealSurgery–AllComers
• VerticalPartialLaryngectomies– VerticalHemilaryngectomy– Frontolateralverticalhemilaryngectomy.– Posterolateralverticalhemilaryngectomy– Extendedverticalhemilaryngectomy– EpiglotticLaryngoplasty
• HorizontalPartialLaryngectomies– Supraglotticlaryngectomy
• SupracricoidPartialLaryngectomyw/Cricohyoido‐Epiglottopexy
SupragloNcLaryngectomy
• Patientselection– younger– vigorous– strongmotivation– goodpulmonaryreserve
• Musttoleratethemild‐to‐moderateaspiration• COPD(maynixthedeal)• Evenwithgastrostomy
– ‐salivaryaspirationmaybeover‐whelming
IssuesaberSupragloNcLaryngectomy….
• Vocalquality– BetterthanTEP?– Predictorsofsuccess?
• Woundhealing/stabilization– irradiation
• ProlongedNGT/PEGuse– extentofremovalofthearytenoid– asymmetricremovalofthefalsecords– remember:atleastoneSLNisresected– resectionofhyoid&BOTmayNOTberelatedtoswallowingoutcome
Limita<onstoSupragloNcLaryngectomy
• Failedfull‐courseradiationforsupraglotticlesions– increasedriskbecauseofunrecognizedsubmucosaltumorspread– originaltumorcon`igurationvs.recurrenttumordimensions
• Thyroidcartilageinvasionoranteriorcommissureinvolvement– tumorhasbrokentheanteriorinnerperichondrialsheath– standardcartilagecutsforpartialsurgeryarehighrisk
• Cricoidcartilageinvolvement– severedysphagia‐laryngealpreservation– bilateralarytenoidinvolvement:absolutecontraindication(Biller)
NodalMetastasisinSupragloNcSCC:Outcomes
• Snydermanetal:– decreasedsurvivalinpatientswithECSwithinNM
• Myersetal:– Nodalmetastasis
• 84%ofpatientswithoutNMsurvivedatleast2years• vs.46%ofpatientswithNMsurvived2years
• Ofpatientsw/recurrenceintheneck,9(64%)hadECS• 71%whodevelopeddistantmetastasishadhistologicevidenceofECS
Myers et al. Management of carcinoma of the supraglottic larynx: evolution, current concepts and future trends. Laryngoscope 1996; 106:559
SupragloNcSCCandSurvival
Myers et al. Management of carcinoma of the supraglottic larynx: evolution, current concepts and future trends. Laryngoscope 1996; 106:559
Two‐YearSurvivalRatesofSupragloNcCarcinomabyStage
Conclusions
• Progress?• HPV?• Anatomy(period!)• Multi‐disciplinaryapproach• EarlyglotticSCC:Slaughter’sHypothesis• VAstudy• RTOG• TLM
References• Forastiereetal.ConcurrentChemotherapyandRadiotherapyforOrganPreservationinAdvanced
LaryngealCancer.NEJM.Volume349:2091‐2098;2003.• TheDepartmentofVeteransAffairsLaryngealCancerStudyGroup.Inductionchemotherapyplus
radiationcomparedwithsurgeryplusradiationinpatientswithadvancedlaryngealcancer.NEJM.Volume324:1685‐1690,1991.
• Boccaetal.Extendedsupraglotticlaryngectomy.Reviewof84cases.AnnOtolRhinolLaryngol1987;96:384.
• Hinnietal.TransoralLaserMicrosurgeryforAdvancedLaryngealCancer.ArchOtolaryngolHeadNeckSurg.2007;133(12):1198‐1204.
• Hoffmanetal.LaryngealcancerintheUnitedStates:changesindemographics,patternsofcare,andsurvival.Laryngoscope.2006Sep;116(9Pt2Suppl111):1‐13.
• Blackwelletal.Laryngealdysplasia:epidemiologyandtreatmentoutcome.AnnOtolRhinolLaryngol.1995Aug;104(8):596‐602.
• Cummings:Otolaryngology,HeadandNeckSurgery.4thEd‐2005‐Mosby,Inc.Philadelphia,Pennsylvania.
• Bailey’s:HeadandNeckSurgery,Otolaryngology.3rdEd‐2005–Lippincott,Williams&Wilkins,Inc.Philadelhpia,Pennsylvania.
• Billeretal.Hemilaryngectomyfollowingradiationfailureforcarcinomaofthevocalcords.Laryngoscope.80(2):249‐53,1970Feb.
• Myersetal.Managementofcarcinomaofthesupraglotticlarynx:evolution,currentconceptsandfuturetrends.Laryngoscope1996;106:559.
• Snydermanetal.Extracapsularspreadofcarcinomaincervicallymphnodes:impactuponsurvivalinpatientswithcarcinomaofthesupraglotticlarynx.Cancer.1985;56:1597‐1599.
• McGavranetal.Theincidenceofcervicallymphnodemetastasefromepidermoidcarcinomaofthelarynxandtheirrelationshiptocertaincharacteristicsoftheprimarytumor.Cancer1961;14:55‐66.