Delays in the health care system for children,

www.jped.com.br

ORIGINAL ARTICLE

Delays in the health care system for children,

adolescents, and young adults with bone tumors in Brazil ^夽

Nathalie V. Balmant

, Neimar de Paula Silva

, Marceli de O. Santos

, Rejane de S. Reis

, Beatriz de Camargo

aInstitutoNacionaldeCâncer,CursodePós-Graduac¸ão,RiodeJaneiro,RJ,Brazil

bInstitutoNacionaldeCâncer,CentrodePesquisa,RiodeJaneiro,RJ,Brazil

cInstitutoNacionaldoCâncer,DivisãodeVigilânciaeAnálisedeSituac¸ãoCoordenac¸ãodePrevenc¸ãoeVigilância,RiodeJaneiro, RJ,Brazil

dFundac¸ãodoCâncer,RiodeJaneiro,RJ,Brazil

Received14February2018;accepted3July2018 Availableonline1August2018

KEYWORDS Brazil;

Diagnosisdelay;

Treatmentdelay;

Healthcaresystem;

Bonetumors

Abstract

Objective: Toidentifydelaysinthehealthcaresystemexperiencedbychildrenandadolescents andyoungadults(AYA;aged0---29years)withosteosarcomaandEwingsarcomausinginformation fromtheBrazilianhospital-basedcancerregistries.

Methods: Patient data were extracted from 161 Brazilian hospital-based cancer registries between2007and2011.Hospital,diagnosis,andtreatmentdelayswereanalyzedinpatients withoutaprevioushistopathologicaldiagnosis.Referral,hospital,andhealthcaredelayswere calculatedforpatientswithaprevioushistopathologicaldiagnosis.Thetimeintervalwasmea- suredindays.

Results: Therewasnodifferencebetweengenders inoveralldelays.Alldelaysincreasedat olderages.Patientswithoutaprevioushistopathologicaldiagnosishadthelongesthospitaldelay whencomparedtopatientswithaprevioushistopathologicaldiagnosisbeforefirstcontactwith thecancercenter.PatientswithEwingsarcomahadlongerreferralandhealthcaredelaysthan thosewithosteosarcomawhohadaprevioushistopathologicaldiagnosisbefore firstcontact withthecancercenter.TheNorthandNortheastregionshadthelongestdiagnosisdelay,while theNortheastandSoutheastregionshadthelongesttreatmentdelay.

夽 Pleasecitethisarticleas:BalmantNV,SilvaNP,SantosMO,ReisRS,CamargoB.Delaysinthehealthcaresystemforchildren,adolescents, andyoungadultswithbonetumorsinBrazil.JPediatria(RioJ).2019;95:744---51.

∗Correspondingauthor.

E-mail:bdecamar@terra.com.br(B.deCamargo).

https://doi.org/10.1016/j.jped.2018.07.003

0021-7557/©2018SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Healthcaredelayinbonetumors 745 Conclusion: Healthcaredelayamong patientswithapreviousdiagnosiswaslonger,andwas probablyassociatedwiththetimetakenfortoreferraltocancercenters.Patientswithouta previoushistopathologicaldiagnosishadlongerhospitaldelays,whichcouldbeassociatedwith possibledifficultiesregardingdemandandhigh-costprocedures.Despitelimitations,thisstudy helpsprovideinitialknowledgeaboutthehealthcarepathwaydelaysforpatients withbone cancerinsideseveralBrazilianhospitals.

©2018SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/

4.0/).

PALAVRAS-CHAVE Brasil;

Atrasono diagnóstico;

Atrasono tratamento;

Sistemadesaúde;

Tumoresósseos

Atrasosnosistemadesaúdeparacrianc¸as,adolescenteseadultosjovenscom tumoresósseosnoBrasil

Resumo

Objetivo: Identificaratrasosnosistemadesaúdeemcrianc¸aseadolescenteseadultosjovens (AAJ;até29anos)comosteossarcomaesarcomadeEwingcominformac¸õesdosregistrosde câncerdebasehospitalardoBrasil.

Métodos: Osdadosdospacientesforamextraídosde161registrosdecâncerdebasehospitalar brasileirosentre2007e2011.Osatrasosnohospital,nodiagnóstico enotratamentoforam analisadosempacientessemumdiagnósticohistopatológicoanterior.Osatrasosnoencamin- hamento,nohospitalenosistemadesaúdeforamcalculadosparapacientescomdiagnóstico histopatológicoanterior.Ointervalodetempofoimedidoemdias.

Resultados: Nãohouvediferenc¸aentreossexosnosatrasosemgeral.Todososatrasosaumen- taramnafaixaetáriamais velha.Ospacientessemum diagnósticohistopatológicoanterior apresentaramoatrasohospitalarmaislongoemcomparac¸ãocomospacientescomdiagnóstico histopatológicoanteriorantesdoprimeirocontatocomocentrodecâncer.Ospacientescom sarcomadeEwingapresentaramatrasosnoencaminhamentoenosistemadesaúdemaislongos doqueoscomosteossarcoma,queapresentaramdiagnósticohistopatológicoanteriorantesdo primeirocontatocomocentrooncológico.AsregiõesNorteeNordesteapresentaramoatraso maislongonodiagnóstico,aopassoqueasregiõesNordesteeSulapresentaramoatrasomais longonotratamento.

Conclusão: Oatrasonosistemadesaúdeentreospacientescomdiagnósticoanteriorfoimaior e provavelmente associado ao tempo de encaminhamento para os centros oncológicos. Os pacientessemum diagnósticohistopatológicoanteriorapresentaram atrasosmais longosno hospital,oquepodeserassociadoapossíveisdificuldadescomrelac¸ãoàdemandaeaosproced- imentosdealtocusto.Apesardaslimitac¸ões,nossoestudoajudaafornecerumconhecimento inicialsobreosatrasosnosistemadesaúdeparatratamentodepacientescomcânceremvários hospitaisbrasileiros.

©2018SociedadeBrasileiradePediatria.PublicadoporElsevierEditoraLtda.Este ´eumartigo OpenAccesssobumalicenc¸aCCBY-NC-ND(http://creativecommons.org/licenses/by-nc-nd/4.

0/).

Introduction

Bonecancersarerelativelyuncommon,accountingforonly 0.2%ofhumanneoplasia.However,youngpatientsaremore affected,andtheetiologyisunknown.¹Approximately60%

of primarybone cancer occursin peopleyounger than 45 years.²The mostincident morphologicalsubtypesofbone cancer among children and adolescentsand young adults (AYA)areosteosarcoma(OS)andEwingsarcoma(ES).^1,3

InBrazil, twocooperativegroups havewell-established treatment protocols for these subgroups of bone cancer, which were created throughan initiative developed by a groupofpediatric oncologists:theBrazilianOsteosarcoma TreatmentGroup(BOTG) andBrazilianCollaborativeStudy Groupfor EwingSarcomaFamilyTumors(Grupo deEstudo

Colaborativo Brasileiro para Tratamento dos Tumores da FamíliaSarcomadeEwing---EWING1).^4,5

Since 1989, all of the Brazilian population is entitled to free health care at the primary, secondary, and ter- tiary levels through the national health system (Sistema ÚnicodeSaude[SUS]). Primary care is composedof units such as the Family Health Program created in 1994 and emergencycare units. A patient withsuspicion of cancer shouldbereferredtoaspecializedcenter(secondarylevel) where high-cost procedures areperformed, such ascom- putedtomography,magneticresonanceimaging,andbiopsy, ifnecessary.Tertiarycareincludesspecializedhospitaland treatment centers where patients should receive therapy fromamultidisciplinaryteam.^6---8

Somepediatriconcologycentershaveadoptedthispath- wayand receive patients only after a diagnosis is made,

Previous histopathological

diagnosis

First contact at cancer center

Histopathological diagnosis at the

cancer center Treatment

Health Care Delay

Referral Delay Diagnosis Delay Treatment Delay

Hospital Delay

Figure1 Diagnosisdelayincancercarepathways,adaptedfromDang-TanandFranco.⁹

while others receive patients when there are suspicious symptoms.Thereisnoregularprocedureor carepathway forchildrenwithcancerinBrazil;however,thecarepath- way may be influenced by several factors. The patient’s family’sinvolvementinthehealthcaresystemis verysig- nificantbecausetheyaretheoneswhorecognizethefirst symptoms of cancer.⁹ Moreover, the professional’s knowl- edge,theprimaryandsecondarycareinfrastructure,aswell asthedistancefromthepatient’sresidencetospecialized centersmay alsobe associatedwith delaysin the cancer caretreatmentpathway.⁸

Delays in the health care system are an important concernduetotheassociationbetweensocioeconomicsta- tus and health care providers, as well as biologic tumor characteristics.^10---13

Theterm‘‘delay’’isusedtodesignatethetimeinterval, whichmaydifferforeachstudy.Thereisnoconsensusabout theexactnumberofdaysthatshouldbeconsideredadelay.⁹ Differentdefinitionsofdelayrelatedtothehealthcaresys- temareusedinliterature,includingpatientdelay(interval betweenthefirstsymptomsandthefirstmedicalcontact);

firstdiagnosis delay (intervalbetween the firstsymptoms andafirstdiagnosis);referraldelay;doctordelay(interval betweenthefirstmedicalcontactandaprecisediagnosis);

hospitaldelay;andtreatmentdelay.9,11,14---16

Thelongestdiagnosisdelaysarereportedforbonecan- cer, carcinomas, and retinoblastoma.^11,16 Some studies in Brazilhavedescribedpatientdelaysamongthosewithbone tumors.^12,17 The mean time from the onset of symptoms todiagnosis in patients registered at BOTG was 129 days (median:90days)andwasnotcorrelatedwiththepresence ofmetastases,tumorsize,orsurvival.⁴Thesedatasuggest thatthe stage of disease dependsmore onthe biological propertiesofthetumorthanonlatediagnosis.

Theaimofthisstudywastoidentifydelaysinthehealth caresystemforchildrenandAYA(0---29years)withOSand ES,usinginformationfromBrazilian hospital-basedcancer registries(HBCRs).

Materials and methods

Agegroupwasclassifiedas0---14years(children)and15---29 years (AYA). As it is known, the term AYA is not clearly definedinliterature.Amongpublications,thedefinitionfor

adolescentsandyoungadultswithcancermostusedinthe literatureisbetween15and29years.

Patient data wereextracted from 161 Brazilian HBCRs between 2007 and 2011.¹⁸ Afterdownloading each of the databases, data was transferred into a database in SPSS (IBMSPSSStatisticsforWindows,version20.0.NY,USA)to provide statisticalanalysis.Patient informationfromeach registry included gender, age group (0---14 years; 15---19 years;and20---29years);subtypeofbone cancer(OS;ES);

previous histopathological diagnosis (yes or no); date of resultsofhistopathologicaldiagnosisperformedbeforethe firstconsultationat acancer center;dataoffirstmedical contactatthecancercenter,dateofresultsofhistopatho- logicaldiagnosisperformedatacancercenter;anddateof treatmentinitiationatacancercenter.Unfortunately,infor- mationontheonsetofsymptomswasnotavailable,soitwas notpossibletoevaluatepatientdelay.

Theterm‘delay’wasusedtodesignatethetimeinter- valmeasuredindayswithoutjudgmentofdelay.^9,16Referral delaywasdefinedasthetimebetweenthedateofthepre- vious histopathological diagnosis and first contact at the cancer center. Diagnosis delay was defined as the time between the first medicalcontact andthe histopatholog- ical diagnosis performed at the cancer center. Treatment delaywasdefinedasthetimebetweenthehistopathologi- caldiagnosisdoneatthecancercenterandtheinitiationof treatment.Hospitaldelaywasdefinedasthetimebetween thedateofthefirstcontactatthecancercenterandtreat- mentinitiationatacancercenter.Healthcaresystemdelay wasdefinedasthetimebetweentheprevioushistopatho- logical diagnosis performed elsewhere and the initiation of treatment at the cancer center (Fig. 1). There were 2008casesofchildren,adolescents,andyoungadults(0---29 years) selected across the five main geographic regions of Brazil (North, Northeast, Southeast, South, and Mid- west).Patientswhohadundergoneanytreatment(except histopathologicaldiagnosis)elsewherewereexcluded.This studyalsoexcludedcaseswithmissinginformationregarding previous diagnosis or treatment. There were 1868 eligi- ble cases. Patients were divided into two groups: Group 1 included patients without a previous histopathological diagnosis, and Group 2 included patients with a previ- ous histopathological diagnosis (biopsy) before their first contactatacancercenter.

Diagnosisandtreatmentdelayswerecalculatedforthe patients in Group 1only. Referral and health caresystem

Healthcaredelayinbonetumors 747

2,008 patients 112 patients excluded

(with previous treatment elsewhere)

1,896 patients

Group 1 1,264 patients

28 patients excluded (without information about previous diagnosis and treatment) 1,868

patients

Group 2 604 patients

Diagnosis Delay

1,257^a patients

Treatment Delay

1,240^b patients

Hospital Delay 1,247^c patients

Hospital Delay

588^e patients Referral

Delay

582^d patients

Health Care Delay

573^f patients

a7 cases without date of diagnosis.

b24 cases without date of diagnosis and/or date of initiation to treatment.

c17 cases without date of initiation of treatment.

d22 cases without date of diagnosis.

e16 cases without date of initiation of treatment.

f 31 cases without date of diagnosis and/or without date of treatment.

Figure2 Patientswithbonetumors selectedfromtheBrazilian HBCRsaccordingtoinformationavailable.Group1, patients withoutprevioushistopathologicdiagnosis;Group2,patientswithprevioushistopathologicdiagnosis.

delaywerecalculatedinGroup2only.BothGroups1and2 wereincludedintheanalysisofhospitaldelay.Thenumber ofpatientsexperiencingeachtypeofdelaydiffereddueto missingdataorerrorsinthedataentry(Fig.2).

The median and 25thand 75th percentiles of time (in days)werecalculatedfordelayoverallandamongthefol- lowingcategories:gender,agegroup,bonecancersubtype, and Brazilian geographic region.SPSS (IBM SPSS Statistics for Windows,version 20.0. NY,USA) wasusedto test the equalityofeach delay withinsubgroupsof selectedvaria- bles(sex, agegroup,typeoftumor, andregion)usingthe Mann---Whitney and Kruskal---Wallis tests. The significance levelwasconsideredasp<0.05.

This study was approved (1.368.120) by the Research EthicsCommitteeofInstitutoNacionaldeCâncerJoséAlen- carGomesdaSilva(INCA).

Results

Amajority of the1868 patients weremale (58.9%), aged between0and14years(45.8%)withadiagnosisofosteosar- coma(72.8%),withoutaprevioushistopathologicaldiagnosis (67.7%),andweretreatedintheSoutheastregion(45.6%;

Table1).

The distribution of delay times was expressed as the medianand25thand75thpercentilesfordelaysaccordingto gender,agegroup,bonetumorsubtype,andBraziliangeo- graphicregion,whichcanbeseeninTable1.Intheoverall analysis,therewasnodifferenceindelaysbetweengenders.

Therewerestatisticallysignificantdifferencesinalldelays accordingtoage.Patientsaged20---29yearshadthelongest delays.

BalmantNVetal.

Table1 Numberanddistributionofallcasesincludedinstudy;mediandelays,25thand75thpercentiles(indays)accordingtoclinicalandsociodemographicvariablesfor bothgroupsofpatients.

n(%) GROUP1 GROUP2

Diagnosis Treatment Hospital Referral Hospital Healthcare

delay delay delay delay delay delay

n Median

(Q1---Q3)

n Median

(Q1---Q3)

n Median

(Q1---Q3)

n Median

(Q1---Q3)

n Median

(Q1---Q3)

n Median

(Q1---Q3) Overall 1868 1257 9(3---23) 1210 12(3---27) 1247 26(14---48) 582 15(7---31) 588 10(3---25) 573 32(15---56) Gender

Male 1100(58.9) 743 9(3---24) 718 13(2---27) 736 27(15---50) 341 15(7---32) 350 10(2---26) 340 32(15---58) Female 768(41.1) 514 9(3---21) 492 11(3---24) 511 25(13---44) 241 15(7---31) 238 11(4---24) 233 32(16---53)

p=0.228^a p=0.624^a p=0.064^a p=0.798^a p=0.567^a p=0.738^a

Agegroup

0---14years 855(45.8) 597 8(3---18) 578 10(3---22) 593 23(13---38) 242 13(6---28) 251 10(3---23) 243 29(14---48) 15---19years 620(33.2) 396 9(4---22) 380 12(2---27) 394 25(14---49) 214 15(7---30) 215 8(3---23) 210 32(15---53) 20---29years 393(21.0) 264 13(5---36) 252 18(4---41) 260 40(21---72) 126 23(9---52) 122 15(5---39) 120 45(26---91)

p<0.05^b p<0.05^b p<0.05^b p<0.05^b p<0.05^b p<0.05^b Bonetumor

Ostesarcoma 1360(72.8) 902 9(4---23) 872 12(3---27) 898 26(15---48) 434 14(6---29) 439 10(4---24) 429 30(15---51) Ewingsarcoma 508(27.2) 355 11(3---25) 338 11(3---25) 349 25(12---46) 148 20(9---47) 149 11(2---29) 144 41(17---75)

p=0.368^a p=0.571^a p=0.129^a p<0.05^a p=0.941^a p<0.05^a

Region

North 109(5.8) 62 13(1---31) 51 8(0---28) 62 23(5---53) 47 18(7---52) 46 13(3---39) 46 44(24---76)

Northeast 527(28.2) 342 17(7---35) 327 12(0---28) 342 36(22---63) 165 14(6---32) 172 12(3---26) 159 33(14---56) Southeast 852(45.6) 589 7(3---16) 576 14(6---28) 582 24(14---44) 259 14(6---28) 257 12(5---26) 256 31(16---54)

South 276(14.8) 195 7(2---15) 189 7(0---19) 192 18(8---34) 76 18(9---36) 78 6(1---15) 77 30(14---48)

Midwest 104(5.6) 69 11(6---26) 67 4(0---17) 69 22(10---32) 35 20(7---45) 35 9(1---17) 35 29(14---71)

p<0.05^b p<0.05^b p<0.05^b p=0.174^b p<0.05^b p=0.198^b

Group1,patientswithoutpreviousdiagnosis;Group2,patientswithapreviousdiagnosis.

a p-Value:Mann---Whitneytest.

b p-Value:Kruskal---Wallistest.

Healthcaredelayinbonetumors 749

Male

Female

Ewing sarcoma

North Northeast Southeast South Midwest Ostesarcoma

0-14 years 15-19 years 20-29 years Group 2

Group 1

Group 2 Group 1

Group 2 Group 1 Group 2 Group 1

0 20 40 60 80 100

0 20 40 60 80 100 0 20 40 60 80 100

0 20 40 60 80 100 p < 0.05

p < 0.05

p < 0.05

p < 0.05 p < 0.05

p < 0.05

p < 0.312 p < 0.05 p < 0.05 p < 0.05 p < 0.05 p < 0.05

Figure3 Mediandelays,25thand75thpercentiles(indays)ofhospitaldelayaccordingtoclinicalandsociodemographicvariables inbothgroupsofpatients.

Thereweredifferencesamongdiagnosisandtreatment delaysbetweenBraziliangeographicregions.TheNortheast hadthelongestdiagnosisdelay,whiletheSoutheasthadthe longesttreatmentdelay(Table1).InGroup2(withprevious histopathological diagnosis), patients with Ewing sarcoma had a longer referral and health care delay than those with osteosarcoma (Table 1). Patientswithout a previous histopathologicaldiagnosis(Group1)hadalongerhospital delaythanpatientswithaprevioushistopathologicaldiagno- sisthatwasperformedbeforetheirfirstcontactatacancer center(Group2;Fig.3).

Discussion

Understandingthedeterminantsalongthecancercarepath- wayisessentialtoimprovestrategiesthatminimizedelays.

The pathway to cancer care is often not straightforward and includes the onset of first symptoms, first investiga- tion,referral toacancer center, definitivediagnosis, and the initiation of treatment.¹⁹ The present study’s path- waystartsafterthehistopathologicdiagnosisor whenthe patient reaches the cancer center, so that it is possible to calculate referral, diagnosis, treatment, hospital, and health care system delays as described in Fig. 1. It was notpossibletoanalyzedelaysregardingthefirstsuspicions of cancer both by family members (or patients) and pri- mary attending physicians. Therefore, an analysis of the completecare pathwaywasnotpossible,jeopardizingthe results.However,healthcaresystemdelaysmayberelated tobureaucraciesassociatedwithproviders,suchasadmin- istrativeprocessesorthediagnosticinfrastructure.

InBrazil,aswellasotherdevelopingcountries,referral delaycanbeaffectedbythehealthcaresystemtakingtoo long toschedule amedical appointmentat a hospital for tertiaryattention. Diagnosisdelay can beassociated with errorsthatoccur inthedifferentialdiagnosisina primary healthcenteroradelayinperformingabiopsy.Treatment delaysmaybeduetothenumberofhospitalbedsavailable andhospitalization, as well asthe number of specialized professionalsatahospital.^13,17

Thelackofstandardizedtimeintervalsusedindifferent studies leads to several controversies that make compar- isonswithotherstudiesintheliteraturedifficult.Diagnosis orpatientdelay is commonlycalculatedasthe timefrom thefirstsymptomstodiagnosisinseveralstudies.^11,17,20The impact of a diagnosis delay on the prognosis of children andadolescentswithcancer isstillcontroversial. Insome types of tumors (e.g., retinoblastoma, Wilms’ tumor), a shorterintervalbetweentheonsetofsymptomsanddiag- nosisreflectsabetterprognosis.^21,22 Patientdelay(ortime fromthefirstsymptomstodiagnosis)inchildrenandadoles- centswithbonetumorshasnotbeenassociatedwithlower survivalrates.^4,20,23

Youngadults aged20---29 years had significantlylonger delays.Aprevious study demonstratedthatmost patients olderthan18yearsinBrazilaretreatedinmedicaloncol- ogywards.²⁴AsdescribedinCanada,adolescentstreatedat adultcenters reportlonger waitingtimes between health careevents.¹⁰AlldelayswerehigherinAYApatients,which can in part be justifiedby the number of patients and a lackofbedsinmedicaloncologywards.Thelongerdiagno- sisdelay inAYAalsomaybeassociatedwithdifficultiesin histopathologicaldiagnosisduetotherarityofbonetumors inthisage group.²⁵ Bleyersuggeststhat oneofthe major

factorsinlongerdelaysforAYAistheirincreasingautonomy overtheirownhealthcaredecisions.²⁶

The population’s access to healthcare has increased greatlyinthepast30yearssincethecreationoftheSUSin Brazil.ThedataweretakenalmostentirelyfromtheHBCRs ofinstitutionslinkedtotheSUS.Thecountryisdividedinto fivegeographicalregions,whichhavedifferencesindemo- graphic,economic,social,cultural,andhealth conditions.

TheBrazilianhealthsystem’schallengesincludethecontrol ofcostsandaccesstocomprehensivecare,andcoordination withprimaryhealthcare.Socioeconomicandotherdispari- tiesamongregionsarestilllarge,affectingthehealthcare system.^6---8Moreover,previousstudiesdemonstratedadeficit inaccesstocancertreatmentforchildrenandadolescents livingintheNorth,wherepatientsmayhavetotravellong distances to access specialized treatment. Many patients andtheir familieshave tomove to receive treatment for theirdisease,andmayprovidefalseinformationtofacili- tateaccesstospecializedwards, reflectingtheinequality betweendifferentregions.^8,27

Among patients without a previous histopathological diagnosis,thelongestdiagnosisdelayoccurredintheNorth- eastregion.Bonetumorsfrequentlyrequirediagnostictests inspecializeddiagnosis centersbeforethefirsttreatment can be administered. The availability of equipment to performCTscansdiffers amongregions(NorthandNorth- east,0.7/100,000inhabitants;Southeast,0.9/100,000;and South,1.4/100,000). Treatment and hospital delays were longerin the Southeastand Northeast regions.The South regionhadtheshortesthospitaldelayinbothpatientgroups.

Thenumberofhospitalbedscouldaffectdelaysinpatient treatment.TheSoutheastregion,whichis themostpopu- lated,hadthelowestnumberofbedsperinhabitant,while theSouthregionhadthehighestnumberofbeds.²⁸

Hospitaldelaywasanalyzedinbothpatientgroupsand therewasasignificantdifferenceinoveralldelay.Patients with a previous histopathological diagnosis had a shorter timefromthefirst contactat acancer center tostarting treatment,exceptintheNorthregion.Despitethefactthat treatmentstarts sooner,itis wellknownthat initialdiag- nosisin a specializedcancer centercan improvesurvival.

Biopsyisafundamentalsteptoadequatetreatmentforbone tumors.Inappropriatebiopsytechniquesinbonetumorscan predispose tolocal relapse.Biopsies should be done with sufficientmaterialtoreachaprecisediagnosis.^29,30There- fore,specializedcentersmayrequestsliderevisioninthose patients with a previous histopathological diagnosis. This candelay the onsetof treatmentdue toa longerwaiting time,althoughitisimportanttoavoidmisdiagnosis.

Themedianoveralldiagnosisdelay(ninedays)andtreat- mentdelay (12days) wereslightly higher thanin Canada (four and seven days, respectively), but lower than in developingcountries suchasNigeria(40daysof diagnosis delay).^17,31

Amongpatientswithaprevioushistopathologicaldiagno- sisofbonetumor,itwasobservedthatthemedianoverall referraldelaywas15days.InCanada,thisintervalwasabout 5---12days.^10,17Therewerenodifferencesinreferraldelays accordingtoBrazilian regions,but therewasa difference inreferraldelayamongbonetumorsubtypes.Patientswith Ewingsarcomaexperiencedsignificantlylongerdelays;how- ever,itispossiblethatthisresultisbychance.Amajordelay

inEwingsarcomaisdescribedinseveralstudiesduetothe difficultly in recognizing specific symptoms and the need for more expertise in histopathologic diagnosis.^11,32 How- ever,studiesarenecessarytoinvestigatethedetailsabout differencesinreferralamongsubgroupsofbonetumors.

There wasa median of 32 days for health care delay, which ranged from 29 to 44 days according to Brazilian regionsinpatientswithaprevioushistopathologicaldiagno- sis.Inotherwords,treatmentinacancercenterisdelayed morethana month.Sincethehospitaldelayin thisgroup wasnot longer,it canbeassumed that referralto cancer centersispossiblythemaincauseofthisdelay.Patientswho wereadmittedtocancercenterswithoutahistopathologi- caldiagnosis(Group1)startedtreatmentafteramedianof 26days.Thisdelaycouldbeassociatedwithpossiblediffi- cultiesinperformingthebiopsyduetodemandthatexceeds thecapacityofsurgicalcenters,andtoalackhigh-costpro- ceduresperformedatthehospitals.Aspreviousdiscussed, biopsyperformed atacancercenterisimportanttoavoid misdiagnosis.

Amajorlimitationofthisstudyisthatthereisnoinfor- mationaboutfirstsymptomsandthefirstmedicalcontact before reachingthe cancer center. Anothermajor limita- tion is that this is a retrospective study, usingsecondary databaseinformationfrom116BrazilianHBCRswithincom- plete recordsand with a possible lack of standardization regarding classificationof variables. Despite these limita- tions, the authors believe that these data provide initial knowledge about the health care pathways amongdiffer- entBrazilian geographicregionsanddifferentagegroups.

Further studies are necessary to better investigation this issue.

Funding

NVB hasa scholarship fromthe National Institute ofCan- cer--- INCA/MS. BDChasascholargrantfromtheNational CouncilforScientificandTechnologicalDevelopment(Con- selhoNacionaldeDesenvolvimentoCientíficoeTecnológico, CNPq,Brasília; #306291/2014-2) and fromthe Foundation for Support of Research, Rio de Janeiro (Fundac¸ão de Amparo à Pesquisado Estado do Rio de Janeiro, FAPERJ, RiodeJaneiro;#212989-2016).

Conflicts of interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgements

TheauthorswouldliketothankalltheHBCRcoordinatorsin Brazilwhocontributedtothedatasetsandmadethiswork possible.

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