Braz. j. . vol.82 número6

(1)

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Audiological

profile

of

patients

treated

for

childhood

cancer

夽

,

夽夽

Patricia

Helena

Pecora

Liberman

a,∗

,

Maria

Valéria

Schmidt

Goffi-Gomez

a

,

Christiane

Schultz

a

_,

_Paulo

_Eduardo

_Novaes

b

_,

_Luiz

_Fernando

_Lopes

c

a_Núcleo_de_Audiologia_do_A.C._Camargo_Cancer_Center,_São_Paulo,_SP,_Brazil b_Hospital_Vitoria,_Santos,_SP,_Brazil

c_Hospital_de_Câncer_de_Barretos,_Departamento_de_Pediatria,_Barretos,_SP,_Brazil

Received15June2015;accepted9November2015 Availableonline13April2016

KEYWORDS

Radiotherapy; Ototoxicity; Chemotherapy; Cisplatin; Hearingloss; Hearing

Abstract

Objective: Tocharacterizethehearinglossaftercancertreatment,accordingtothetypeof treatment,withidentificationofpredictivefactors.

Methods:Twohundredpatientswhohadcancerinchildhoodwereprospectivelyevaluated.The meanageatdiagnosiswas6years,andattheaudiometricassessment,21years.The treat-ment oftheparticipantsincludedchemotherapywithoutusingplatinumderivativesorhead andneckradiotherapyin51patients; chemotherapyusingcisplatin withoutradiotherapyin 64patients;headandneckradiotherapywithoutcisplatinin75patients;andacombined treat-mentofheadandneckradiotherapyandchemotherapywithcisplatinintenpatients.Patients underwentaudiologicalassessment,includingpuretoneaudiometry,speechaudiometry,and immittancemetry.

Results:Thetreatmentinvolvingchemotherapywithcisplatincaused41.9%and47.3%hearing lossintherightandleftear,respectively,witha11.7-foldhigherriskofhearinglossinthe rightearand17.6-foldhigherintheleftearversuspatientsnottreatedwithcisplatin(p<0.001 andp<0.001,respectively).Childrenwhosecancerdiagnosisoccurredaftertheageof6have shownanincreasedriskofhearinglossvs.childrenwhosediagnosisoccurredunder6yearsof age(p=0.02).

夽 _Please_cite_this_article_as:_Liberman_PH,_Goffi-Gomez_MV,_Schultz_C,_Novaes_PE,_Lopes_LF._Audiological_profile_of_patients_treated_for

childhoodcancer.BrazJOtorhinolaryngol.2016;82:623---9.

夽夽_This_study_was_conducted_in_the_A._C._Camargo_Cancer_Center.

∗_{Corresponding}_author.

E-mail:[email protected](P.H.Liberman). http://dx.doi.org/10.1016/j.bjorl.2015.11.021

(2)

Conclusion:Theauditoryfeaturefoundafterthecancertreatmentwasasymmetricalbilateral sensorineuralhearingloss.Chemotherapywithcisplatinprovedtobeariskfactor,whilehead andneckradiotherapywasnotcriticalfortheoccurrenceofhearingloss.

© 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

PALAVRAS-CHAVE

Radioterapia; Ototoxicidade; Quimioterapia; Cisplatina; CDDP;

Perdaauditiva; Audic¸ão

Perfilaudiológicodepacientestratadosdecâncernainfância

Resumo

Objetivo:Caracterizarasalterac¸õesauditivasapósotratamentodocâncer,segundootipode tratamentoidentificandoosfatorespreditivos.

Método: Foramavaliadosprospectivamenteduzentospacientesquetiveramcancerna infân-cia. A idade médiaao diagnóstico foi de 6anoseà avaliação audiométricade 21 anosde idade.Otratamentoincluiuquimioterapiasemusodederivadosdeplatinaouradioterapiaem cabeçaepescoçoem51pacientes;quimioterapiacomusodecisplatinasemradioterapiaem 64pacientes;radioterapiaemcabeçaepescoçosemcisplatinaem75pacientes;e10pacientes receberamotratamentocombinadoderadioterapiaemcabeçaepescoçoequimioterapiacom cisplatina.Ospacientesforamsubmetidosàavaliaçãoaudiológicaincluindoaudiometriatonal, audiometriavocaleimitanciometria.

Resultados: Otratamentoenvolvendoquimioterapiacomcisplatinalevoua41,9%e47,3%de perdaauditivanaorelhadireitaeesquerda,respectivamente,apresentandorisco11,7vezes maiordedesenvolverperdaauditivanaorelhadireitae17,6vezesnaorelhaesquerdadoque aquelesquenãoreceberamcisplatina(p<0,001ep<0,001;respectivamente).Crianc¸ascujo diagnósticodocâncerocorreuapósos6anosdeidademostrarammaiorriscodeapresentar perdaauditivadoquecrianc¸asmenoresdoque6anosdeidade(p=0,02).

Conclusão:Acaracterísticaaudiológicaencontradaapóstratamentooncológicofoiperda audi-tivasensorioneuralbilateral simétrica. Aquimioterapiacomcisplatinamostrouser fatorde risco,enquantoaradioterapiaemcabeçaepescoçonãofoideterminanteparaaquisiçãoda perdaauditiva.

© 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Publicado por Elsevier Editora Ltda. Este é um artigo Open Access sob uma licença CC BY (http:// creativecommons.org/licenses/by/4.0/).

Introduction

Overthelasttwodecades,childhoodcancermortalityhas

decreasedsignificantly;however,itstillrepresentsthe

sec-ondleading causeof deathin Brazil.1 _Currently,_with_the

advances in diagnosis, improved treatments, and

appro-priate clinical support, an increase in the cure rate of

malignanciesinchildhoodisapossibility.2_In_the_face_of_an

increasingsurvivalrate,theseindividualsarenowmonitored

forseveralyears.Thus,itispossibletoobservetheimpact

oflateeffectsoftreatment onthequalityoflifeofthese

youngadults.

Theuseofdifferenttreatmentmodalities(surgery,

radio-therapy,andchemotherapy)andthecombinationofthese

modalitiescontributetoimprovedresults,bothin

control-lingthediseaseandinimprovingsurvivalrates.3

Amongtheototoxicdrugs,cisplatinisanantineoplastic

agentwithprovenanti-tumoractivity,butwhichmayhave

ototoxicityasasideeffect;thedoserelatedtoriskhasbeen

describedasbeing400mg/m2_.2,4,5

Head and neck radiotherapy concomitantly employed

with cisplatin (cis-diamminedichloroplatinum [CDDP])

increasesthelikelihoodofseverehearingloss.6,7_However,

when the drug is administered alone and in lower doses

(50---60Gy),noclinicallysignificanthearinglossoccurs.8,9

Ototoxicity, i.e., the effect represented by an injury

to the peripheral organ of hearing, is characterized by

an irreversible descending bilateral sensorineural hearing

loss.10,11_The_incidence_of_the_hearing_loss_is_quite_variable,

duetothemethodofdrugadministration,tumorlocation,

state of renal function, patient’s age, associated drugs,

radiotherapy, pre-existing hearing loss, cumulative dose,

totaldoseoftreatment,andindividualsusceptibility.12,13

Thisstudywasconductedwiththeaimofcharacterizing

theaudiologicprofileof patientswhohadcancerin

child-hood andwereout ofcancer treatment for at leasteight

years;torelatethehearinglossfound withrespecttothe

typeoftreatmentandage;andtoidentifypredictivefactors

forhearingloss.

Methods

Weprospectivelyevaluatedchildrenwhohadcancertreated

between2000and2004,andwhohadcompletedtreatment

(3)

groupofpediatricstudiesonthelateeffectsofcancer

treat-ment.Patientswithhistoryofpreviousotologicdiseaseor

who hadbeen submitted toa surgery involving the

audi-torysystemwereexcluded.Thestudywasapprovedbythe

ResearchEthicsCommitteeoftheinstitutionunderthe

pro-tocol549/03.Eligiblepatientsortheirlegalguardianswere

consultedonthepossibilityofparticipatinginthestudy,and

wereaskedtosigntheinformedconsent.

Patients were interviewed at the Pediatric Outpatient

Clinicinordertoinvestigatethepresenceofhearing

com-plaintsandthenwerereferredtoahearingevaluationinthe

institution’sAudiology Service, regardlessof thepresence

ofhearingcomplaints.Otoscopywasconductedbeforethe

testand,ifthepatienthadcerumenoranysuspicionand/or

obstructionthatpreventedthetest,he/shewasreferredto

theotorhinolaryngologistbeforeevaluation.

For hearing assessment, auditory quantification tests

(pure tone audiometry and speech audiometry) and

evaluation tests of the tympanic-ossicularsystem

(immit-tancemetry)wereperformed.Tothisend,aMadsenOrbiter

922audiometerandaMadsenZodiac901immittancemeter

wereused.

The doseofCDDPreceivedbytheparticipantswas

cal-culatedandadjustedbythepediatriconcologistforabody

surface area of 1m2_. _The _clinical _records _of _all _patients

whounderwentheadandneckradiotherapywereanalyzed,

takingintoaccountthesideonwhichradiotherapywas

per-formed and whether the auditory system wasincluded in

theradiationfield.Thetotaldoseandtheestimateddose

ofradiation reachingtheauditorysystem werecalculated

for eachearbyaradiation oncologist,basedonthe

plan-ning form. The variable‘‘radiation reachingthe auditory

system’’ was categorized as: no Rxt, Rxt≤4000cGy, and

Rxt>4000cGy.9,14

Patientswerestudiedaccordingtothetypeoftreatment

performed,basedontheuseofchemotherapywithCDDPor

headandneckradiationtherapy.

HearinglosscriteriawerebasedontheBureau

Interna-tionald’Audiophonologie---BIAP,15 _which_considers_hearing

loss as the presence of pure tone thresholds >20dB in

0.5---4kHzfrequencies.

Statisticalanalysis

Toidentifyhearinglosspredictors,adichotomousvariable

(yes/no)wascreated,andhearinglosswasdiagnosedonly

inlight of changesin thefrequencies from0.25 to4kHz.

Hearinglossat6and8kHzwasnotincludedinthestatistical

analysis,duetotheminorhandicapthattheselossescause

indailylife.16,17

Thevariable‘‘ageat diagnosis’’wascategorizedas≤6

yearsand>6years,basedonthemedianofthevaluesfound.

Measuresofcentraltendencyandofdispersionfor

quan-titativevariablesandabsoluteandrelativefrequenciesfor

categoricalvariableswerecalculated.Inordertoverifythe

associationamongindependentvariablesandhearingloss,

theassociativechi-squaredtestorFisher’sexacttest(when

atleastoneoftheexpectedfrequencieswas<5)wasused.

Toidentifyindependentriskfactorsforoccurrenceof

hear-ing loss, logistic regression (with raw and adjusted odds

ratios and their respective 95% confidence intervals) was

used.Forallstatisticaltests,anerror˛=5%wasestablished,

i.e.,theresultswereconsideredstatisticallysignificantat

p<0.05.

Results

Theselectedsampleincluded200patientstreatedfor

child-hoodcancer, whowereoutof treatmentduring thestudy

period.Table1showsthedistributionaccordingtothe

pri-marytumorandthetypeoftreatmentused.Inthisstudy,51

participantsdidnotundergoheadandneckradiotherapyand

werenotmedicatedwithCDDP,64receivedchemotherapy

withCDDP and did not undergo head and neck

radiothe-rapy, 75 underwent head and neck radiotherapy without

chemotherapywithCDDP,andtenpatientsunderwenthead

andneckradiotherapyandchemotherapywithCDDP.Inmost

Table1 Distributionofpatients,accordingtothetypeofprimarycanceratdiagnosisandtreatmenttype(GEPETTO2000---2004).

Malignantneoplasm w/oRxtw/oCDDP CDDP Rxt Rxt+CDDP Total

n(%) n(%) n(%) n(%) n(%)

Bonetumor 8(15.7) 39(60.9) 1(1.3) 0(0.0) 48(24.0)

Leukemias 1(2.0) 0(0.0) 43(57.3) 0(0.0) 44(22.0)

Lymphomas(NHL,HL) 14(27.5) 0(0.0) 10(13.3) 0(0.0) 24(12.0) Retinoblastoma 8(15.7) 1(1.6) 10(13.3) 5(50.0) 24(12.0) Germcelltumor 2(3.9) 12(18.7) 0(0.0) 0(0.0) 14(7.0) Kidneytumors 12(23.5) 1(1.6) 0(0.0) 0(0.0) 13(6.5) Softtissuesarcomas 3(5.8) 3(4.6) 3(4.0) 2(20.0) 11(5.5)

CNStumor 0(0.0) 0(0.0) 4(5.3) 2(20.0) 6(3.0)

SNStumor(neuroblastoma) 1(2.0) 4(6.3) 0(0.0) 1(10.0) 6(3.0)

Unspecified 0(0.0) 1(1.6) 4(5.3) 0(0.0) 5(2.5)

Carcinomas 2(3.9) 1(1.6) 0(0.0) 0(0.0) 3(1.5)

Livertumors 0(0.0) 2(3.1) 0(0.0) 0(0.0) 2(1.0)

Total 51(100) 64(100) 75(100) 10(100) 200(100)

(4)

Table2 Meansandstandarddeviationsoftheradiationdosage(Rxt)andofcisplatin(CDDP)usedaccordingtothetypeof treatmentfortheright(RE)andleft(LE)ear(GEPETTO2000---2004).

Typeoftreatment n Rxttotaldose(cGy) RERxtdose(cGy) LERxtdose(cGy) CDDPdose(mg/m2₎

w/oRxt,w/oCDDP 51 --- --- ---

---CDDP 64 --- --- --- 647.4±326.5

Rxt 75 2996.8±1427.8 1894.8±1544.3 1821.5±1540.8 ---Rxt+CDDP 10 4214.0±678.9 2292.0±1744.2 1524.0±1692.7 668.1±260.7

Table3 Distributionofpatientswhometthehearinglosscriteriainrelationtothefactorsstudied:sex,age,radiation,and chemotherapywithCDDP(GEPETTO2000---2004).

RE Total pa _LE _Total _pa

w/oloss n(%)

Withloss n(%)

n w/oloss

n(%)

Withloss n(%)

n

Gender 0.525 0.062

Male 86(82.7) 18(17.3) 104 88(84.6) 16(15.4) 104

Female 76(79.2) 20(20.8) 96 71(74.0) 25(26.0) 96

Age 0.001 0.001

≤6years 100(90.1) 11(9.9) 111 98(88.3) 13(11.7) 105

>6years 62(69.7) 27(30.3) 89 61(68.5) 28(31.5) 95

Rxt 0.025 0.020

w/oRxt 103(76.9) 31(23.1) 134 103(74.6) 35(25.4) 138

≤4000cGy 52(92.9) 4(7.1) 56 50(92.6) 4(7.4) 54

>4000cGy 7(70.0) 3(30.0) 10 6(75.0) 2(25.0) 8

Chemo <0.001 <0.001

w/oCDDP 119(94.4) 7(5.6) 126 120(95.2) 6(4.8) 126

WithCDDP 43(58.1) 31(41.9) 74 39(52.7) 35(47.3) 74

Total 162(81.0) 38(19.0) 200 159(79.5) 41(20.5) 200

Boldedprefertostatisticalsignificance(p<0,05). a_Statistics_according_to_the_chi-squared_test.

cases,childrentreatedbyRxtwithoutCDDPhadadiagnosis

ofleukemiaorretinoblastomaandweretreatedwith

mega-voltage radiation. For patients who received CDDP+Rxt,

the total radiation dose was higher (4214.0±678.9cGy)

vs. patients who received only Rxt (2996.8±1427.8cGy)

(Table2).

Table3showsthat104(52%)participantsofthesample

weremaleand96(48%)werefemale.

Hearing

loss

characterization

PatientswhoreceivedCDDPorCDDP+Rxtwereaffectedby

asymmetricalbilateralsensorineuralhearinglossat4-,6-,

and8-kHzfrequencies.Hearinglossdidnotoccurincancer

patientswhodidnotreceivearisk-to-hearingtreatmentor

headandneckRxtasasingletreatment(Fig.1).

Identification

of

predictive

factors

for

hearing

loss

InthecomparisonamongthethreegroupswithoutRxt,and

withRxt upto 4000 or above4000cGy,both tothe right

(p=0.025) and to the left (p=0.020) side, a statistically

0

10

20

30

40

50

60 8 kHz 6 4 2 1 0.5 0.25

w/o Rxt and w/o CDDP RE w/o Rxt and w/o CDDP LE

CDDP RE

CDDP LE

Rxt RE

Rxt LE

Rtx + CDDP RE

Figure1 Meanaudiometricconfigurationofhearing thresh-olds by type of treatment. CDDP, cisplatin; Rxt, radiation treatment;RE,rightear;LE,leftear.

significantdifferencewasobserved.Itisnotpossible,

how-ever,tostatethattheRxtfactorhasinfluencedthehearing

lossbecause,thevaluesforthepercentageofhearingloss

comparingthegroupthatdidnotreceiveRxtvs.thosethat

receivedmorethan4000cGyaresimilar.Thus,itisbelieved

thatthestatisticalsignificanceisduetothelower

(5)

Table4 Multipleanalysisofpredictivefactorsofhearinglossintheright(RE)andleft(LE)ear.

Ear Variables Categories RawOR AdjustedOR 95%CIadjustedOR p

RE CDDP No 1.0 1.0 Reference

Yes 12.2 11.7 4.2;32.1 <0.001a

Rxt w/oRxt 1.0 1.0 Reference

≤4000cGy 0.3 0.9 0.2;3.3 0.894

>4000cGy 1.4 4.3 0.8;24.1 0.196

Age(years) ≤6 1.0 1.0 Reference

>6 3.9 2.7 1.1;6.4 0.028

LE CDDP No 1.0 1.0 Reference

Yes 17.9 17.6 6.0;51.4 <0.001b

Rxt w/oRxt 1.0 1.0 Reference

≤4000cGy 0.2 0.9 0.2;3.4 0.912

>4000cGy 0.9 3.9 0.5;31.2 0.192

Age(years) ≤6 1.0 1.0 Reference

>6 3.5 2.1 0.9;5.0 0.084

OR,oddsratio;CDDP,cisplatin;Rxt,radiotherapy. a _{Hosmer---Lemeshow}_test₍_p₌_0.856).

b _{Hosmer---Lemeshow}_test₍_p₌_0.459).

4000cGy, therebydifferingfromtheother twogroups, as

canbeseeninTable3.

Multivariate

analysis

of

predictive

factors

for

hearing

loss

Inthemultivariateanalysis(consideringthosepatientswho

did not use CDDP as a control group), use of CDDP and

age at the time of diagnosis were predictive factors for

hearingloss.Childrenwhosetreatmentincludedtheuseof

CDDPshowedan11.7-foldincreasedriskforhearinglossin

theright earanda17.6-foldincreasedriskintheleftear

(p<0.001forbothears),comparedtochildrenwhodidnot

useCDDP.Diagnosisbeforetheageof6yearsimparteda2.7

timeshigherriskforhearinglossintherightear(p=0.02),

comparedwithchildrenaged≤6years(Table4).

Inthemultivariateanalysis,thedoseofradiotherapywas

notariskfactorforhearinglosswhenpatientswhodidnot

receiveRxtwereusedasacontrolgroup.

Discussion

This study aimed to establish a relationship of hearing

changesfoundbytypeoftreatmentandage,andto

iden-tifypredictive factorsof hearingloss inpatients whohad

cancer in childhoodandhad completedcancer treatment

severalyearsbefore.Todefinewhichtreatmentimpliedrisk

ofhearingloss,aseparationwasrequiredbetweentheears,

consideringthattheincidenceofradiationvariedwiththe

tumorsite.

Thisstudyfoundapredominanceofexamswith

thresh-oldswithinthenormalrangeinpatientswhodidnotundergo

treatmentwithCDDP.Conversely,patients whousedCDDP

or CDDP+Rxt showed a predominance of bilateral

sym-metrical sensorineural hearing loss at 4-, 6-, and 8-kHz

frequencies.11,12,18---22_It_is_possible_to_infer_that_hearing_loss

isrelatedtothetypeofcancertreatment,evenconsidering

thattheseareindividualsassessedmanyyearsaftertheend

oftheirtherapy,sincethegroupwhose treatmentdidnot

involveCDDPorRxt,underthesameconditions,showedno

hearingloss.

Paulino etal.,23 _Johannesen _et _al.,24 _Low _et _al.,8 _and

Dell’Aringaetal.9 _reported_that _doses _between₄₀₀₀ _and

6000cGywereriskdosagesforhearingloss,andsuggested

audiological monitoring. Treatment with Rxt in head and

neck tumors can cause other ear disorders such as

oti-tisexterna, serousotitismedia,25 _necrosis_of _the_external

auditory canal, and osteoradionecrosis of the temporal

bone.14,24,26 _In _the _present _series, _leukemias _were

preva-lentinpatients whoweretreatedwithRxtwithout CDDP,

andtheseindividualsshowednohearingloss,whichis

con-sistentwiththeresultsreportedinthestudybyThibadoux

etal.27_Indeed,_the_dosage_of_radiation_penetrating_the_right

(2292.0±1744.2cGy)andtheleft(1524.0±1692.7cGy)ear

wasoflow-riskforallpatientswhounderwentRxt.Table3

showsthat92.9%ofpatientswhoreceiveddosesofradiation

therapybelow4000cGy didnotshowhearingloss,

justify-ingthesignificantassociation.Inthemultivariateanalysisof

predictivefactorsforhearingloss,Rxtwasnotariskfactor

forhearingloss(Table4).

PatientstreatedwithCDDPandCDDP+Rxtreceivedhigh

doses of CDDP --- higher than the dose considered a risk

for hearing loss (≥400mg/m2_). _In _this _series, _the _mean

dose of CDDP in patients treatedwith chemotherapy was

650mg/m2_,_and_in_individuals_who_received_CDDP₊_Rxt,_the

dose was670mg/m2_._Li _et_al.22 _pointed _out_the

relation-shipbetweendose ofCDDPandhearingloss,withdosages

≥400mg/m2 _showing _a _higher _risk _for _hearing _loss.

Stud-iesusingconventionalfrequencies(0.25---8kHz)forhearing

evaluationrevealavariationof20---70%intheincidenceof

hearingloss.28 _This _change _occurs_due _to _several_factors,

including: the assessed frequencies, age of the

individ-uals, dosage of CDDP, drug dosing schedule, and criteria

used to define hearing loss. The present study found a

prevalenceof41.9%and47.3%forREandLE,respectively,

basedonhearinglosscriteriaat frequenciesfrom0.25 to

(6)

Lietal.22_indicated_that_there_is_a_greater_risk_for_hearing

lossinchildrenunder5yearsofage.Brocketal.,18 _Simon

etal.,29 _and_Gunn_et_al.30 _found_no_{statistically}_significant

relationshipbetweentheuseofCDDPandage.

In the present sample, it wasfound that the age of 6

yearsatthetimeofcancerdiagnosisimparteda2.7times

higherriskforhearingloss(p=0.02)comparedwithchildren

≤6yearsofageatdiagnosis,butonlyfortherightear,with

atendencyfortheleftear(OR=2.1;p=0.08).Thisfinding

maybeduetothisseriesofpatients,whohadtheirhearing

loss concentrated in osteosarcoma diagnoses, more often

establishedinadolescence(Table1).

Thepresentstudyfoundnostatisticallysignificant

rela-tionshipforgender;however,Yanceyetal.28_reported_that

genderandcumulativedose arethemostimportant

clini-calmarkersofototoxicity.Theseverityofototoxicitymay

beinverselyrelatedtoage atthetimeof treatment,and

youngerchildrenhavegreaterdegreesofhearinglossafter

treatment.28 _Ondrey _et_al.31 _believe_that_the _combination

of these two treatments (Rxt+QT) will be the best

can-certreatmentinthefuture;however,boththerapiescause

ototoxiceffects.

Inthisstudy,thesample ofpatientsundergoinga

com-bined treatment (Rxt+CDDP) was small (n=10); but the

samedegreeandtypeofhearinglosswasfoundinpatients

whounderwentchemotherapywithCDDPwithoutRxt.This

findingdemonstratesthat,inthisstudy,Rxtwasnotarisk

factorforhearingloss,butCDDPwas.

Considering the impact of hearing loss, even if

sub-clinical, on the linguistic, pedagogical, and cognitive

developmentofchildrentreatedforcancerinchildhood,32

andconsideringalsothatstudiesdemonstratingasignificant

otoprotectiveeffecthavenotyetbeenpublished,33_the_most

importanttoolinthefollow-upofthesepatientsiscertainly

monitoring.34

Conclusion

The hearing loss identified in cancer patients, examined

yearsafterthecompletionoftreatmentwassensorineural,

bilateral,andsymmetrical,andpredominantlyaffectedthe

frequenciesof4,6,and8kHz.

ChemotherapywithCDDPwasdemonstratedtobearisk

factorforacquisitionofhearingloss,whileheadandneck

radiationtherapywasnotdecisive.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgements

The authors thank Dr. Karina B. Ribeiro for her valuable

assistanceindataanalysis.

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