Oral cavity squamous cell carcinoma: factors related to occult lymph node metastasis

Full text

(1)

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Oral

cavity

squamous

cell

carcinoma:

factors

related

to

occult

lymph

node

metastasis

夽,夽夽

André

Fernandes

d’Alessandro

a

,

Fábio

Roberto

Pinto

b

,

Chin

Shien

Lin

b

,

Marco

Aurélio

Vamondes

Kulcsar

b

,

Cláudio

Roberto

Cernea

a

,

Lenine

Garcia

Brandão

a

,

Leandro

Luongo

de

Matos

b,

aDisciplineofHeadandNeckSurgery,FaculdadedeMedicina,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil bInstitutodoCâncerdoEstadodeSãoPaulo(ICESP),SãoPaulo,SP,Brazil

Received12November2013;accepted6July2014 Availableonline30March2015

KEYWORDS Carcinoma; Squamouscell; Mouth; Lymphatic metastasis; Prognosis Abstract

Introduction:Electiveneckdissectionisrecommendedincases oforalcavitysquamouscell carcinomawithoutlymphnodemetastasisbecauseoftheriskofoccultmetastasis.

Objective:Thepresentstudyaimedtoevaluatepredictivefactorsforoccultlymphnode metas-tasisinpatientswithoralcavitysquamouscellcarcinomatreatedwithelectiveneckdissection andtheirimpactonoverallanddisease-freesurvival.

Methods:Fortysurgicallytreatedpatientswereretrospectivelyincluded.

Results:Tencases(25%)hadlymphatic metastasis.Of thestudiedvariables,perineuraland angiolymphaticinvasioninadditiontotumorthicknesswerestatisticallyassociatedwithlymph nodemetastasis.Onlyangiolymphaticinvasion was identifiedasanindependent risk factor foroccultmetastasisinthelogisticregression(OR=39.3;p=0.002).Therewasnoassociation betweenoverallanddisease-freesurvivalwiththepresenceofoccultlymphnodemetastasis.

Conclusion:Metastaticdiseaseratewassimilartothatfoundintheliterature.Perineuraland angiolymphaticinvasionandtumorthicknesswereassociatedwithoccultmetastasis,butonly angiolymphaticinvasionshowedtobeanindependentriskfactor

© 2015Associac¸ãoBrasileira de Otorrinolaringologiae CirurgiaCérvico-Facial. Publishedby ElsevierEditoraLtda.Allrightsreserved.

Pleasecitethisarticleas:d’AlessandroAF,PintoFR,LinCS,KulcsarMA,CerneaCR, BrandãoLG,etal.Oralcavitysquamouscell carcinoma:factorsrelatedtooccultlymphnodemetastasis.BrazJOtorhinolaryngol.2015;81:248---54.

夽夽Institution:InstitutodoCâncerdoEstadodeSãoPaulo(ICESP),SãoPaulo,SP,Brazil.Correspondingauthor.

E-mail:lmatos@amcham.com.br(L.L.deMatos). http://dx.doi.org/10.1016/j.bjorl.2015.03.004

1808-8694/©2015Associac¸ãoBrasileiradeOtorrinolaringologia eCirurgiaCérvico-Facial. PublishedbyElsevierEditoraLtda.All rights reserved.

(2)

PALAVRAS-CHAVE Carcinoma; Célulasescamosas; Boca; Metástaselinfática; Prognóstico

Carcinomaespinocelulardacavidadeoral:fatoresrelacionadosàpresenc¸ade metástaseslinfonodaisocultas

Resumo

Introduc¸ão: Oesvaziamentocervicaleletivoérealizadodemaneirasistemáticanoscasosde carcinomaespinocelulardacavidadeoralsemlinfonodosclinicamentecomprometidosdevido àaltaincidênciademetástasesocultas.

Objetivo: Avaliarpacientescomcarcinomaespinocelulardecavidadeoraltratadoscom esvazi-amentocervicaleletivoquantoafatorespreditivosparaocorrênciademetástasesocultaseo impactodasmesmasnasobrevivênciaglobalelivredeprogressãodestespacientes.

Método: Quarentapacientescirurgicamentetratadosforamavaliadosemestudoretrospectivo.

Resultados: Dezcasos(25%)apresentarammetástasesocultas.Dasvariáveisanalisadas,invasão perineuraleangiolinfáticaetambémaespessuratumoralforamestatisticamentesignificantes àanáliseunivariada.Apenasainvasãoangiolinfáticafoifatorindependentederiscode metás-tasesocultaspelaregressãologística(OR=39,3;p=0,002).Apresenc¸ademetástaseocultanão apresentoudiferenc¸aestatisticamentesignificanteemrelac¸ãoàstaxasdesobrevivênciaglobal elivredeprogressão.

Conclusão:Aincidênciademetástaseocultafoisemelhanteàliteratura.Ainvasãoperineural, angiolinfáticaeaespessuratumoralforamfatoresassociadosàpresenc¸ademetástaseoculta, porémapenasainvasãoangiolinfáticaapresentou-secomoumfatorderiscoindependentepara ocorrênciadofenômeno.

©2015Associac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.Publicado por ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Squamouscellcarcinoma isthemost commonhistological

type of cancer of the oral cavity, and has an important

and well-established pattern of dissemination to cervical

lymphnodes.1Even inpatientsclinicallywithout evidence

ofmetastaticlymphnodes(N0),electiveneckdissectionin conjunctionwithresectionoftheprimarytumor,ispartof thestandard treatmentof thediseasebecausetheriskof occultmetastasisisgreaterthan20%.1---6

Several studies have triedto assessfactors that would predict occult metastases and their influence on survival rates,suchastumorthickness,perineuralinvasionand angi-olymphatic invasion.1,7---10 In attempts to reduce surgical

morbidity,somehaveproposedalternativestoelectiveneck dissection, such as sentinel lymph node mapping11,12 and

evenavoidinganysurgicalapproachtotheneckinselected cases;13,14 thelatter hasthe poorestsurvival results.5,15,16

Thus,elective neckdissection currentlyremains themost widelyusedtreatment.

The present study aimed to evaluate the risk of the presenceofoccultlymphnodemetastasesinpatientswith squamous cell carcinoma of the oral cavity submitted to resectionandelectiveneckdissection,inordertoidentify factors related to the development of nodal metastases, and to identify its impact on overall and disease-free survival.

Method

This wasa longitudinal historical cohort study that, after approvalbytheEthicsCommitteeofInstitutionalResearch

underNo.507/11,retrospectivelyassessedelectronic medi-calrecords of consecutive patients submitted to primary tumorresectionwithintenttocurecombinedwithelective neckdissectionin patients withoral cavitysquamouscell carcinoma(includingthelip).Fortypatientswereselected fromAprilof2009(beginningoftheHeadandNeckSurgery Service)untilDecemberof2012.

Inclusioncriteriaconsistedofcasesofsquamouscell car-cinoma of the oral cavity, whose initial treatment was a surgicalprocedurewithprimarylesionresectionand elec-tiveunilateralorbilateralneckdissection,dependingonthe lesionlocation,withallpatientsbeingconsideredN0at clin-icalexaminationandpreoperativeimagingtests.Neoplasms inothersitesthantheoralcavitywereexcluded,aswellas otherhistologicaltypes,patientswhohadsuspectedlymph nodedetectedintraoperatively,leadingtoconductchange intoradicaldissection,andpatientssubmittedtoprevious surgical treatment or chemotherapy and/or radiotherapy, evenforneoplasmslocatedatanothersiteintheheadand neck.

Patientswereassessedregarding:

1. Demographicdata:genderandage;

2. Clinicaldata:primarytumorlocation(forthisvariable, majororalcavitysubsitesweredividedintotongue,floor ofthemouth,retromolararea,lip,buccalmucosa,and alveolarborder).Patientswereonlyincludedwith squa-mous cell carcinoma of the lip when it extended to the buccal mucosa, justifying elective neck dissection accordingtotheinstitutionalprotocol;

3. Anatomopathological data:pT stage(analyzed in inde-pendent subgroups and also in pT1 and pT2 vs. pT3

(3)

andpT4aandpT1---pT3vs.pT4astratification),primary tumor thickness (in mm), presence or absenceof per-ineural and angiolymphatic invasion, surgical margins, pN stage,number of lymphnodes in pN+ cases, pres-enceorabsenceofcapsularleakageinmetastaticlymph nodes,andanatomopathologicalstagepergroups(I---IV) accordingtotheclassificationofAmericanjoint Commit-tee onCancer/Union for International CancerControl, UICC/AJCC(7thedition,2010);

4. Surgicaldata:relatedtotheperformedneckdissection; 5. Adjuvant treatments performed: radiotherapy and/or

chemotherapy;

6. Developmentoflocoregionalrecurrence,distant metas-tasis, and second primary tumor, as well as time of occurrenceoftheseevents;

7. Follow-up timein months,requiring a minimum of 12 monthsforpatientswhodidnotdieduringthisperiod; 8. Most recentoncological status (aliveand disease-free,

alivewiththedisease,asymptomaticdead,anddeaddue tocancer).

Statistical analysis was performed asdescribed below. Thevaluesobtainedbythestudy ofeachcontinuous vari-ablewereorganizedandexpressedasmean andstandard deviation,whereasqualitativevariableswereexpressedas absoluteandrelativefrequencies.Sampledistributionwas definedasparametricusingtheKolmogorov---Smirnovtest. Comparisonsof the frequency of a phenomenon between groupsofqualitativevariableswereperformedusingFisher’s exacttestorthechi-squaredtest.Thecomparisonbetween themeans ofacontinuousvariablewithparametric distri-butionbetweentwogroupswasperformedusingStudent’s

t-test.Thelogisticregressionmodelwasusedinthe multi-variateanalysis,establishingvaluesofoddsratio(OR)and 95%confidenceinterval(95%CI).

TheKaplan---Meiermethodwasusedforsurvivalanalysis andcomparisonofgroupswasperformedusingthelog-rank test.AllanalyseswereperformedusingStatisticalPackage fortheSocialSciences,(SPSSstatisticalsoftware),version 17.0(SPSSInc---Illinois,USA),withasignificancelevelof5% (p<0.05).

Results

Ofthe40patients,35(87.5%)weremalesandmeanagewas 60years(minimum40andmaximumof89years,standard deviationof12.9years).

The most often affectedsubsiteswere thetongue and thefloorofthemouth(65%)andtherewasapredominance of advanced stages (stages III and IV=52.5%). As for the histologicalcharacteristicsofprimarytumors,meantumor thicknesswas1.4±1.2cm;infivecases(12.5%)thefinal sur-gicalmarginswereconsideredinvolved;24tumors(60%)had perineuralinvasionandnine(22.5%)showedangiolymphatic invasion.Meanfollow-upwas18monthsandninecasesof diseaseprogressionwereidentified(fiveexclusively locore-gionalrecurrences,onecaseofpulmonarymetastasiswith controlledprimarysiteandneck, andthreepatients with both)andmorethanhalf ofthepatients (52.5%)required adjuvant treatment. The descriptive data of the entire seriesareshowninTable1.

Table1 Demographic,clinical,andanatomopathological data(n=40). Variable Absolute frequency Relative frequency(%) Gender Male 35 87.5 Female 5 12.5 Subsite Tongue 15 37.5

Floorofthemouth 11 27.5 Retromolararea 7 17.5 Buccalmucosaorlipwith

buccalextension 6 15.0 Alveolarborder 1 2.5 Anatomopathological 24 60.0 Perineuralinvasion 9 22.5 Angiolymphaticinvasion 24 63.2 Tumorthickness>7mm (n=38)a 35 87.5 Freemargins 13 32.5 pT 9 22.5 pT1 4 10.0 pT2 14 35.0 pT3 30 75.0 pT4a 4 10.0 pN 6 15.0 pN0 3 30.0 pN1 12 30.0 pN2b 7 17.5 Extracapsularleakage (n=10) 5 12.5 Stage 16 40.0 I II III IVa Follow-up 2 5.0

Secondprimarytumor 21 52.5

Adjuvanttreatment 14 35.0 Isolatedradiotherapy 7 17.5 Chemoradiation 9 22.5 Recidivism 8 20.0 Locoregional 4 10.0 Distantmetastasis 9 22.5 Death

a Thickness:mean±standarddeviation=1.4±1.2cm.

Regarding the analysis of neck dissection, 14 patients underwentbilateralsurgery,astheprimarytumorsurpassed theanatomicalmidline,totaling54dissections.The mean number of dissected lymph nodes was 27.2±11.4. Most cases (87.5%) underwentdissection at levelsI, II, and III, but five patients were submitted to level IV dissection due to intraoperative decision of the attending surgeon, and there were no occult metastases to lymph nodes at that levelin anyof thesecases. Tenpatients(25.0%) had occult lymphnode metastasesinthe anatomopathological

(4)

Table2 Univariateanalysisoffactorsrelatedtothe pres-enceofoccultlymphnodemetastasis.

Comparison Lymphnode metastasis/total(%) p Gender 1.000a Male 9/35(25.7) Female 1/5(20.0) Ageb 0.240b

Absenceoflymphnode metastasis

61.5±12.5 Presenceoflymphnode

metastasis

58.2±14.4

Subsite 0.544c

Tongue 2/15(13.3)

Floorofthemouth 4/11(36.4)

Retromolararea 3/7(42.9) Lip 1/4(25.0) Buccalmucosa 0/2(0.0) Alveolarborder 0/1(0.0) Perineuralinvasion 0.032a No 1/16(6.3) Yes 9/24(37.5) Angiolymphaticinvasion <0.0001a No 3/31(9.7) Yes 7/9(77.8) Tumorthickness>7mm 0.043a No 1/14(7.1) Yes 9/24(37.5) pTdStage 0.230c pT1 1/13(7.7) pT2 2/9(22.2) pT3 2/4(50.0) pT4a 5/14(35.7)

a Fisher’sexacttest.

b Comparisonbetweenmeansofage---Student’st-test. c Chi-squaredtest.

d Note: no statistically significant difference was observed betweenthestratifiedpTstageandthepresenceofoccultlymph nodemetastasis (p=0.274 and p=0.278,respectivelyfor pT1 andpT2vs.pT3andpT4a,andpT1---pT3vs.pT4a).

assessment(Table1),andnoneofthepatientsundergoing bilateralneckdissectionhadN2cstage.

ThevariabletumorthicknesswassubmittedtoROCcurve analysis,anditwasdeterminedthatthebestcutoffforrisk stratification ofoccult lymphnode metastaseswas>7mm (areaundertheROCcurveof68.2%;95%CI:50.3%---86.1%). The univariate analysis,detailed in Table 2, showed that thepresenceofperineuralinvasion(p=0.032;Fisher’sexact test), angiolymphatic invasion (p<0.0001; Fisher’s exact test),andtumorthickness>7mm(p=0.043;Fisher’sexact test)werefactorsrelatedtothepresenceofoccultlymph nodemetastases.

Variables with p<0.20 in the univariate analysis were submittedtoalogisticregressionmodel,showninTable3. It was verifiedthat angiolymphatic invasion wasthe only independent risk factor for the presence of occult lymph

Table3 Multivariateanalysisofriskfactorsforthe pres-enceofoccultlymphnodemetastasis.

Factor OR 95%IC pa Presenceofangiolymphatic invasion 39.3 3.7---420.9 0.002 Presenceofperineural invasion 1.5 0.1---23.7 0.766 Tumorthickness>7mm 11.6 0.7---204.3 0.093 a Logisticregression.

node metastasis (OR=39.3; 95% CI: 3.7---420.9; p=0.002). Asthiswasaretrospectivestudy,thecalculationofpower forthisestimatewasconductedduring theanalysis,using themethodfor cohortstudies. ConsideringtheORof39.3 andtheproportionof25%ofoccultlymphnodemetastases inthisgroup,theinclusionof40patientsdeterminedthat thisestimatedemonstratedpower>90%.

Survival analysisshowed that disease-freesurvival and overallcumulativesurvival(Figure1)were68.2%and64.1%, respectively.Eventhoughtherewasnostatistically signifi-cantdifference,patientswithoccultlymphnodemetastases showeda lowerdisease-freesurvival rate,aloweroverall survival, and a median survival of 28 months in the final analysis,comparedtopatientswithoutthisfactor(Table4;

Figure2).

Discussion

The presence of occult metastases in squamous cell car-cinoma of the oral cavity is very prevalent due to its aggressiveness1 and neck treatment is mandatory, even

in cases without clinical signs of involvement. Surgical treatment has an advantage over radiotherapy, since it establishesthepatient’scompletepathologicalstaging, pre-ventingunnecessaryuseofradiotherapyinsomecases.17

Thissampleshowedaprevalenceofmalepatients,with mosttumorslocatedinthetongueandfloorofthemouth, consistentwiththeliterature.3,7,16 Thepresence ofoccult

metastases in 25% of cases was in agreement with other studies.1,3,4,18 With regard to all cases with positive neck

involvement,it isnoteworthythatthreecaseshad metas-tasisinmorethanonecervicallevel,andinthreecasesthe metastaseswere stages II and/or III, withlevel I disease-free.NopatienthadlevelIVinvolvement.Thisshowsthat althoughsomecasesofskipmetastasesoccurred,dissection atlevelsI---III wouldhavebeensufficienttreatment forall patientsinthisseries.

However,someauthorshavereported3---28%ofaffected lymph nodes at level IV, especially in tongue and floor-of-the-mouth tumors, but studies have disagreed about electivedissection extensiontolevelIVin theoral cavity tumors,withmostofthemfavoringthenon-extension.19---22

It is noteworthy that the present study included 40 con-secutive patients, which at first may be considered a smallsample and a limitation of the study; however, the calculationofpowerofthemainestimateperformed (angi-olymphaticinvasionasan independentrisk factor for the presenceofoccultlymphnodemetastasis)was>90%,which demonstratesthestatisticalsignificanceofthefindings.

(5)

Disease-free survival Cumulative survival 1.0

Survival Function Censored

0.8 0.6 0.4 0.2 0.0 0 10 20

A

B

Time (months) Total follow-up time (months)

30 40 1.0 0.8 0.6 0.4 0.2 0.0 0 10 20 30 40

Survival Function Censored

Figure1 Kaplan---MeierCurves.(A)Cumulativedisease-freesurvivalof68.2%;(B)Cumulativeoverallsurvivalof64.1%.

Table4 Analysisofoverallanddisease-freesurvival.

Variable Events/total Accumulatedsurvival(%) pa

Disease-freesurvival 0.587

Absenceoflymphnodemetastasis 6/30 71.4

Presenceoflymphnodemetastasis 3/10 60.0

Overallsurvival 0.248

Absenceoflymphnodemetastasis 5/30 80.4

Presenceoflymphnodemetastasis 4/10 40.0b

aLog-ranktest.

b Medianofsurvivalattainedat28months.

In the many existing studies, the major risk factors for occult metastases are angiolymphatic invasion, per-ineuralinvasion, and tumor thickness.1,2,4,8,9,17,19 This was

corroboratedbythepresentstudy,butonlyangiolymphatic

invasion was shown to be an independent risk factor of occultmetastases.

Althoughstudiesincreasinglyfocusonthese characteris-ticsaspredictorsoflymphaticdissemination,fromaclinical

Disease-free survival

Overall cumulative survival

1.0 0-censored 0 1 1-censored 0.8 0.6 0.4 0.2 0.0 0 10 20

A

B

Time (months) 30 40 1.0 N+ (1=sim, 0=no) 0.8 0.6 0.4 0.2 0.0 0 10 20

Total follow-up time (months)

30 40

0-censored

0 1 1-censored

N+ (1=sim, 0=no)

Figure2 Kaplan---Meiercurvescomparingthegroupswithabsenceandpresenceofoccultlymphnodemetastasis.(A)Cumulative disease-freesurvivalof71.4%and60.0%,respectively,fortheabsenceandpresenceofoccultlymphnodemetastases(p=0.587 ---log-ranktest);(B)Cumulativeoverallsurvivalof80.4%and40.0%,respectively,fortheabsenceandpresenceofoccultlymphnode metastases(p=0.248---log-ranktest).

(6)

pointofview,exceptforthickness,allarefactorsthatare inaccessibleuntiltumorresectionandthereforemaynotbe usedfor decision-making,suchasnottreatingtheneckor usinglessinvasivetreatmentssuchassentinellymphnode technique. When positron emissiontomography-computed tomography(PET-CT),whichhasbeenincreasinglyusedand studied, is negativefor the neck,it is considered enough evidencetojustifyexpectantconduct,butthepatient sam-plesevaluatedwerefewandfollow-upwasnotlongenough toevaluatesurvivalor morbiditieswhensalvage neck dis-sectionisemployed.19,23

The sentinellymphnode(SLN)techniqueforthe treat-mentofN0patientshasbeenstudiedsincethe1990s.Ithas similarratestoelectiveneckdissectionforthedetectionof occultmetastases.24,25 AEuropeanmulticenterstudy

com-paredtwogroups,oneusingthesentinellymphnodeandone withsystematicextensiontoselectiveneckdissectionwitha follow-upoffiveyears;itfoundcervicalrecurrenceinthree casesconsiderednegativeintheSLNarmbutnorecurrence intheother group.24 Italsoshoweddifferencein

disease-freesurvival,butwithoutstatisticalsignificance.24Another

Europeanstudywithfollow-upof10years,inwhichSLNwas carriedoutwithoutsystematicneckdissectionin 53cases froma totalof 174, showedmethod failurerate of 4.8%, withnegativepredictivevalueof95.2%,consideredbythe authorsimilartothatofelectiveneckdissection.25

Tumor thickness has been widely studied as a predic-tor of cervical lymph node metastases in patients with squamouscellcarcinomaoftheupperaerodigestivetract, especiallybecauseupto40%ofpatientswiththesetumors exhibit occult metastases.26 Huang et al.27 performed a

meta-analysisanalyzingtumorthicknessandtheriskof cer-vicallymphnode metastasis.Theyconcludedthata4-mm cutofffor tumor thicknesswouldbe astrong predictorof thepresenceofoccultcervicallymphnodemetastasis;they foundarateof16.6%amongpatientswithtumorthickness >4mm,comparedto4.5%amongthosewithtumorthickness ≤4mm.

Fukanoetal.28studied34patientswithtonguecarcinoma

treatedwithearlysurgicalresectionswithoutpreoperative therapy.Meantumorthicknesswas6.4mm(0---18.2mm)and 64.7% of patients with tumor thickness >5mm had lymph nodemetastases,comparedto5.9%ofpatientswith thick-ness<5mm.Thepresentstudyestablishedacut-offof7mm as a predictor of occult neck metastases, established by theROCcurveanalysis.Thisindex,slightlyhigherthanthat foundintheliterature,isprobablyduetothefactthatthe presentstudywasperformedinapublicinstitution,inwhich patientspresentwithmoreadvancedneoplasmsatthe ini-tialdiagnosis.Themeantumorthicknesswas14mmand45% ofpatientshadpT3andpT4atumors,whichunfortunately iscomparabletomostBrazilianoncologicalinstitutions,and oneofthelimitationsforcomparisonofresults,especially withinternationalcaseseries.

Thisstudyalsodocumentedasmallproportionofoccult metastasesinpatients withpT1 or pT2stage(17.4%),but thisresultissimilartothatfoundintheliterature.Kelner etal.29foundratesof12.5%and22.4%fortheincidenceof

lymphnodemetastasesinpatientswithsquamouscell carci-nomaoftheoralcavitythatwererespectivelypT1andpT2 (20.5%when thestageswere added).Thus,Poonachaand Go30 question whether elective neck dissection should be

performedin thispopulation despitetherecommendation oftheAmericanprotocol.

Pathologicalfeaturesarevaluableforindicationof adju-vanttreatmentwithradiotherapyand/orchemotherapy,as patientswithknownpresenceofcervical metastaseshave lowersurvivalrates,especiallydisease-freesurvival, com-paredtopatientswithoutneckinvolvement.Theoveralland disease-freesurvivalcurvesshowninthisstudydemonstrate theeffectofthepresenceoflymphnodeinvolvementon dis-easeevolution;evenwhentheinvolvementismicroscopic, the necessary adjuvant therapy is performed. However, thesepatientshaveloweroverallanddisease-freesurvival ratesthanpatientswithtumorsconfinedtotheprimarysite. The fact that the oncological follow-up period of five yearshasyettobecompletedisalimitationofthisstudy. Thisoccurred becausetheInstitute opened in2009; how-ever,theauthorsbelievethatthisfacthaslittleinfluenceon survivalanalysis.Itiswellknownintheliteraturethattumor recurrence occurs mainly in the first year of follow-up. Pintoetal.31 found that92.8%oflocoregionalrecurrence

occurredwithinthefirst12monthsoffollow-upinpatients withsquamouscellcarcinomaoftheoralcavityand orophar-ynx.

Conclusions

Thisstudydemonstratedthattheincidenceofoccult metas-tasesinsquamouscellcarcinomaoftheoralcavitywas25% in a population consisting of 45% pT3 and pT4a patients. Amongthefactorsevaluated,perineuralandangiolymphatic invasionandtumor thickness>7mm wereassociated with thepresenceofoccultneckmetastases,butonly angiolym-phaticinvasionprovedtobeanisolatedriskfactorforthe occurrenceoftheevent. Disease-freesurvival andoverall survivalinthe twogroups exhibiteddifferences,although theywerenotstatisticallysignificant.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

References

1.PimentaAmaralTM,DaSilvaFreireAR,CarvalhoAL,PintoCA, KowalskiLP.Predictivefactorsofoccultmetastasisand prog-nosisofclinicalstagesIandIIsquamouscellcarcinomaofthe tongueandfloorofthemouth.OralOncol.2004;40:780---6. 2.ByersRM,El-NaggarAK,LeeYY,RaoB,FornageB,TerryNH,

etal.Canwedetectorpredictthepresenceofoccultnodal metastasesinpatients withsquamouscarcinoma oftheoral tongue?HeadNeck.1998;20:138---44.

3.Yu S,LiJ,Li Z,ZhangW,ZhaoJ.Efficacyofsupraomohyoid neckdissectioninpatientswithoralsquamouscellcarcinoma andnegativeneck.AmJSurg.2006;191:94---9.

4.Lim YC, Kim JW, Koh YW, Kim K, Kim HJ, Kim KM, et al. Perivascular---submandibular lymph node metastasis in squa-mouscellcarcinomaofthetongueandfloorofmouth.EurJ SurgOncol.2004;30:692---8.

5.Fasunla AJ, Greene BH, Timmesfeld N, Wiegand S, Werner JA, Sesterhenn AM.A meta-analysis of therandomized con-trolledtrialsonelectiveneckdissectionversustherapeuticneck

(7)

dissectioninoralcavitycancerswithclinicallynode-negative neck.OralOncol.2011;47:320---4.

6.El-NaajIA,LeiserY,ShveisM,SaboE,PeledM.Incidenceoforal canceroccultmetastasisandsurvivalofT1-T2N0oralcancer patients.JOralMaxillofacSurg.2011;69:2674---9.

7.JerjesW,UpileT,PetrieA,RiskallaA,HamdoonZ,Vourvachis M,et al.Clinicopathologicalparameters, recurrence, locore-gionalanddistantmetastasisin115T1-T2oralsquamouscell carcinomapatients.HeadNeckOncol.2010;20:2---9.

8.Martínez-GimenoC,RodríguezEM,VilaCN,VarelaCL.Squamous cell carcinomaoftheoralcavity: aclinicopathologicscoring systemforevaluatingriskofcervicallymphnodemetastasis. Laryngoscope.1995;1057Pt1:728---33.

9.MortonRP,FergusonCM,LambieNK,WhitlockRM.Tumor thick-nessinearlytonguecancer.ArchOtolaryngolHeadNeckSurg. 1994;120:717---20.

10.VijayakumarM,BurrahR,SabithaKS,NadimulH,RajaniBC.To operateornottooperateN0neckinearlycancerofthetongue? Aprospectivestudy.IndianJSurgOncol.2011;2:172---5. 11.Paleri V, Rees G, Arullendran P, Shoaib T, Krishman S.

Sen-tinelnode biopsyinsquamous cellcancer oftheoralcavity and oral pharynx: a diagnostic meta-analysis. Head Neck. 2005;27:739---47.

12.GoversTM,HanninkG, MerkxMA,TakesRP,RoversMM. Sen-tinel node biopsy for squamous cell carcinoma of the oral cavityandoropharynx:adiagnosticmeta-analysis.OralOncol. 2013;49:726---32.

13.VandenbrouckC,Sancho-GarnierH,ChassagneD,SaravaneD, CachinY,MicheauC.Electiveversustherapeuticradicalneck dissectioninepidermoidcarcinomaoftheoralcavity:results ofarandomizedclinicaltrial.Cancer.1980;46:386---90. 14.NieuwenhuisEJ,CastelijnsJA,PijpersR,vandenBrekelMW,

Brakenhoff RH, van der Waal I, et al. Wait-and-see policy for the N0neck inearly-stageoral and oropharyngeal squa-mouscellcarcinomausingultrasonography-guidedcytology:is therearoleforidentificationofthesentinelnode?HeadNeck. 2002;24:282---9.

15.FakihAR,RaoRS,PatelAR.Prophylacticneckdissectionin squa-mouscellcarcinomaoforaltongue:aprospectiverandomized study.SeminSurgOncol.1989;5:327---30.

16.Kligerman J, Lima RA, Soares JR, Prado L, Dias FL, Freitas EQ, et al. Supraomohyoid neck dissection in the treatment ofT1/T2squamouscellcarcinoma oforalcavity.AmJSurg. 1994;168:391---4.

17.GendenEM,FerlitoA,SilverCE,TakesRP,SuárezC,OwenRP, etal.Contemporarymanagementofcanceroftheoralcavity. EurArchOtorhinolaryngol.2010;267:1001---17.

18.FerlitoA,SilverCE,RinaldoA.Electivemanagementoftheneck inoralcavitysquamouscarcinoma:currentconceptssupported byprospectivestudies.BrJOralMaxillofacSurg.2009;47:5---9.

19.KowalskiLP,SanabriaA.Electiveneckdissectioninoral carci-noma:acriticalreviewoftheevidence.ActaOtorhinolaryngol Ital.2007;27:113---7.

20.ShahJP,CandelaFC,PoddarAK.Thepatternsofcervicallymph nodemetastasesfromsquamouscarcinomaoftheoralcavity. Cancer.1990;66:109---13.

21.DavidsonBJ,KulkarnyV,DelacureMD,ShahJP.Posteriortriangle metastasesofsquamouscellcarcinomaoftheupper aerodiges-tivetract.AmJSurg.1993;166:395---8.

22.WoolgarJA.Detailedtopographyofcervicallymph-node metas-tasesfromoralsquamouscellcarcinoma.IntJOralMaxillofac Surg.1997;26:3---9.

23.GoshenE,DavidsonT,YahalomR,TalmiYP,ZwasST.PET/CT intheevaluationofpatientswithsquamouscellcancerofthe headandneck.IntJOralMaxillofacSurg.2006;35:332---6. 24.Alkureishi LW, Ross GL,Shoaib T, Soutar DS, Robertson AG,

ThompsonR,etal.Sentinelnodebiopsyinheadandneck squa-mouscellcancer:5-yearfollow-upofaEuropeanmulticenter trial.AnnSurgOncol.2010;17:2459---64.

25.MelkaneAE,MamelleG, WyciskG, TemamS,JanotF, Casir-aghi O, et al. Sentinel node biopsy in early oral squamous cellcarcinomas:a10-yearexperience.Laryngoscope.2012;122: 1782---8.

26.PintoFR,deMatosLL,PalermoFC,KulcsarMA,CavalheiroBG, deMelloES,etal.Tumorthicknessasanindependentriskfactor ofearlyrecurrenceinoralcavitysquamouscellcarcinoma.Eur ArchOtorhinolaryngol.2013;271:1747---54.

27.Huang SH, Hwang D, Lockwood G, Goldstein DP, O’Sullivan B. Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity:ameta-analysisofreportedstudies.Cancer.2009;115: 1489---97.

28.FukanoH,MatsuuraH,HasegawaY,NakamuraS.Depthof inva-sionasapredictivefactorforcervicallymphnodemetastasis intonguecarcinoma.HeadNeck.1997;19:205---10.

29.KelnerN,VartanianJG,PintoCA,Coutinho-CamilloCM, Kowal-ski LP. Does electiveneck dissection in T1/T2 carcinoma of theoraltongueand floorofthemouthinfluencerecurrence andsurvivalrates?BrJMaxillofacSurg.2014,pii:S0266-4356: 00127-2.

30.Poonacha TK, Go RS. Level of scientific evidence underly-ingrecommendationsarisingfromtheNationalComprehensive Cancer Network clinical practice guidelines. J Clin Oncol. 2011;29:186---91.

31.Pinto FR, Matos LL, Palermo FC, Martinez JK, Kulcsar MAV, CavalheiroBG,etal.Tratamentocirúrgicodocarcinoma epi-dermoidedacavidadeoraleorofaringenoInstitutodoCâncer doEstadodeSãoPaulo(ICESP):perfildospacientestratados eresultadosoncológicosiniciais.RevBrasCirCabec¸aPescoc¸o. 2012;41:53---7.

Figure

Updating...