Time to diagnosis of brain tumors in

children: A single-centre experience

Thesymptomsofabraintumorshowabroadvarietyandoccurindifferent
combinations.13Headacheiscommonlynamedasthemainsymptomoccurringin50
90%ofpatients.3,5,7,13,14Mostchildrendevelopadditionalneurologicsymptomswithin4
weeks.4,15,16Thecombinationofheadacheandneurologicfindingsmaybespecificforan
intracraniallesion.5
Ontheotherhand,headacheisacommonsymptomandmostlyharmless.Thereare
approximately5000childrenwithrecurrentheadache,includingabout2000children
sufferingfrommigraineforeverychildwithabraintumor.17
Thesecondmostcommonsymptomisvomitingandnausea.3,5,10Ifotherabdominal
symptoms,suchasabdominalpain,feveroralterationofbowelpattern,arenotfound,a
neurologicalexaminationshouldbeperformed.14,18
Signsandsymptomsofincreasedintracranialpressure(headache,nauseaorvomiting,
papilledema,inyoungerchildrenenlargingoftheheadorseparationofcranialsutures)
arefoundinabout50%ofpatients.2,3,19Lessthanonethirdthoughpresentwiththe
classicaltriadofheadache,recurrentvomitingandpapilledema.13,20Inourcohort,this
triadwasfoundinonly10%ofpatients.
Behavioralsymptomsandlethargyaredescribedinupto50%ofpatients.13,14These
symptomsaredifficulttomeasure.13Nevertheless,lethargyshouldbeconsideredasan
importantsymptomand,especiallywhenoccurringincombinationwithheadacheor
neurologicdisorders,anorganiccauseshouldbetakenintoconsideration.13
Visualdisordersarefoundinapproximately5080%ofpatientswitha
craniopharyngioma.21,22
Endocrinesymptomsarefoundinnearlyallpatientspresentingwith
craniopharyngiomasorpinealregiontumors2123andonethirdofpatientswith
intracranialgermcelltumors.24Theseincludedisordersofgrowthhormone(75%),
gonadotrophin(40%),adrenocorticotropin(25%)andthyrotropin(25%).Diabetes
insipidusneurohormonalisisfoundin17%ofpatientspresentingwitha
craniopharyngioma.22
Mostsymptomsofanintracranialmasscanalsooccurinharmlessdiseases.Themain
challengeforthedoctorfacingachildwithsymptomslikeheadacheorvomitingisto
differentiatebetweenaharmlessillnessandapotentiallylifethreateningcondition.
Awarenessofthebroadvarietyofsymptomsisessential.Mostpatientswithan

intracranialmassmaybeidentifiedbyacarefullytakenhistoryandthoroughclinicaland
neurologicalexamination.4,17
Childrenwithachronicheadacheshouldbereviewedregularly.16Incaseofachanging
patternofheadache,additionalvomitingornausea,furtherinvestigationisindicated.10,16,17
Incaseofaseizure(excepttypicalfebrileseizureswithoutfocalneurologicsymptoms)a
secondaryconvulsionshouldbeexcluded.5,15,25
Ifabraintumorissuspected,neuroimagingshouldbeconductedandcontactbemade
withthenextpediatriconcologyunit.TheMRIscanisthepreferreddiagnostictest.26,27In
Germany,MRIiswidelyavailableandascanshouldbeperformedwithoutrelevanttime
delay,4althoughtheremaybedelayinperformingscansinbabiesandyoungerchildren
requiringsedation.5

DexamethasoneAlleviatesTumor
AssociatedBrain
DamageandAngiogenesis
Childrenandadultswiththemostaggressiveformofbraincancer,malignantgliomasor
glioblastoma,oftendevelopcerebraledemaasalifethreateningcomplication.This
complicationisroutinelytreatedwithdexamethasone(DEXA),asteroidalanti
inflammatorydrugwithpleiotropicactionprofile.Hereweshowthatdexamethasone
reducesmurineandrodentgliomatumorgrowthinaconcentrationdependentmanner.
LowconcentrationsofDEXAarealreadycapableofinhibitinggliomacellproliferation
andathigherlevelsinducecelldeath.Further,theexpressionoftheglutamateantiporter
xCT(systemXc2;SLC7a11)andVEGFAisupregulatedafterDEXAtreatment
indicatingearlycellularstressresponses.However,inhumangliomasDEXAexerts
differentialcytotoxiceffects,withsomehumangliomacells(U251,T98G)resistantto
DEXA,afindingcorroboratedbyclinicaldataofdexamethasonenonresponders.
Moreover,DEXAresistantgliomasdidnotshowanyxCTalterations,indicatingthat
thesegeneexpressionsareassociatedwithDEXAinducedcellularstress.Hence,siRNA
mediatedxCTknockdowningliomacellsincreasedthesusceptibilitytoDEXA.
Interestingly,cellviabilityofprimaryhumanastrocytesandprimaryrodentneuronsis
notaffectedbyDEXA.WefurthertestedthepharmacologicaleffectsofDEXAonbrain
tissueandshowedthatDEXAreducestumorinduceddisturbancesofthe
microenvironmentsuchasneuronalcelldeathandtumorinducedangiogenesis.In
conclusion,wedemonstratethatDEXAinhibitsgliomacellgrowthinaconcentration
andspeciesdependentmanner.Further,DEXAexecutesneuroprotectiveeffectsinbrains

andreducestumorinducedangiogenesis.Thus,ourinvestigationsrevealthatDEXAacts
pleiotropicallyandimpactstumorgrowth,tumorvasculatureandtumorassociatedbrain
damage.

Survival rates for selected childhood brain and

spinal cord tumors
Survivalratesareoftenusedbydoctorsasastandardwayof
discussingapersonsprognosis(outlook).Someparentsmaywant
toknowthesurvivalstatisticsforchildreninsimilarsituations,
whileothersmaynotfindthenumbershelpful,ormayevennot
wanttoknowthem.Ifyoudonotwanttoreadaboutthesurvival
statisticsforbrainandspinalcordtumorsgiveninthenextfew
paragraphs,skiptothenextsection.
The5yearsurvivalratereferstothepercentageofchildrenwho
liveatleast5yearsaftertheircancerisdiagnosed.Ofcourse,
manychildrenlivemuchlongerthan5years(andmanyarecured).
Toget5yearsurvivalrates,doctorshavetolookatchildrenwho
weretreatedatleast5yearsago.Improvementsintreatmentsince
thenmightresultinabetteroutlookforchildrennowbeing
diagnosedwithbraintumors.
ThenumbersbelowcomefromtheCentralBrainTumorRegistry
oftheUnitedStates(CBTRUS)andarebasedonchildrenaged19
oryoungerwhoweretreatedbetween1995and2010.Thereare
someimportantpointstonoteaboutthesenumbers:

Thesenumbersareforsomeofthemorecommontypesoftumors.
Numbersarenotreadilyavailableforalltypesoftumorsthatoccur
inchildren,oftenbecausetheyarerareorarehardtoclassify.

Insomecases,thenumbersincludeawiderangeofdifferenttypes

oftumorsthatcanhavedifferentoutlooks.Forexample,the
survivalrateforPNETsbelowincludesmedulloblastomas,
pineoblastomas,andPNETsinotherpartsofthebrain.
Medulloblastomastendtohaveabetteroutlookthantheother
PNETs.Thereforetheactualsurvivalrateformedulloblastomas
wouldbeexpectedtobehigherthanthenumberbelow,whilethe
numberforotherPNETswouldlikelybelower.
Survivalratesareoftenbasedonpreviousoutcomesoflarge
numbersofchildrenwhohadthedisease,buttheycantpredict
whatwillhappeninanyparticularchildscase.Knowingthetype
ofachildsbraintumorisimportantinestimatingtheiroutlook.
Butmanyotherfactorscanalsoaffectachildsoutlook,suchas
thelocationandextentofthetumorandhowwellitrespondsto
treatment.Eventakingtheseotherfactorsintoaccount,survival
ratesareatbestroughestimates.Yourchildsdoctorknowsyour
childssituationandisyourbestsourceofinformationonthis
topic.