Malignant lesions of the Larynx RPenn 11-12-08 - UCLA Health · 2009-05-16 · Malignant Lesions of...

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


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?


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• 2yearsurvivalrateinìrst2groups(non‐salvagegroups)was68%• laryngealpreservation:possiblein64%ofinductionchemotherapy(41%overall)

• “Theefìcacyofchemotherapyfollowedbyradiotherapy(withsurgicalsalvage)wassimilartothatofsurgeryfollowedbyradiotherapyandofferedtheaddedbeneìtoflaryngealpreservationintwothirdsofthepatientstreatedbythisapproach.“

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.”


Notheydiin’t!!RTOGtrial: Givencomparablesurvivaloutcomesb/wnsurgeryandorgansparingTxthelogicalpreferencemustbeforanonsurgicalorgan‐preservingapproach.

Hinnietal: “Thisviewlargelyignoredtheestablishedroleofcurrent openpartiallaryngectomytechniquesandagrowing expertisewithorgan‐preservingTLMinEuropeandNorth America.Inrespondingtothiscontention….Thedatapresented hereincanspeci`icallycomparetheoutcomesofTLMwith orwithoutadjuvantRTtotheRTOGTrialdata.”


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.

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