What is glioma - European Society for Medical Oncology | …€¦ · What is glioma? Let us explain...

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What is glioma? Let us explain it to you. Glioma ESMO/ACF Patient Guide Series based on the ESMO Clinical Practice Guidelines www.anticancerfund.org www.esmo.org

Transcript of What is glioma - European Society for Medical Oncology | …€¦ · What is glioma? Let us explain...

What is glioma?

Let us explain it to you.

Glioma

ESMO/ACF Patient Guide Seriesbased on the ESMO Clinical Practice Guidelines

www.anticancerfund.org www.esmo.org

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GLIOMA:AGUIDEFORPATIENTS

PATIENTINFORMATIONBASEDONESMOCLINICALPRACTICEGUIDELINESThisguide forpatientshasbeenpreparedby theAnticancerFundasa service topatients, tohelppatients and their relatives better understand the nature of glioma and appreciate the besttreatment choices available according to the subtypeof glioma.We recommend that patients asktheir doctors about what tests or types of treatments are needed for their type of disease. Themedical information described in this document is based on the clinical practice guidelines of theEuropean Society for Medical Oncology (ESMO) for the management of glioma. This guide forpatientshasbeenproducedincollaborationwithESMOandisdisseminatedwiththepermissionofESMO. It has been written by a medical doctor and reviewed by two oncologists from ESMOincludingtheleadingauthoroftheclinicalpracticeguidelinesforprofessionals.Itisalsoreviewedbytwonursesof theEuropeanOncologyNursingSociety (EONS)andbypatient representatives fromESMO’sCancerPatientWorkingGroup.MoreinformationabouttheAnticancerFund:www.anticancerfund.orgMoreinformationabouttheEuropeanSocietyforMedicalOncology:www.esmo.orgForwordsmarkedwithanasterisk,adefinitionisprovidedattheendofthedocument.

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Tableofcontents

Factsheetaboutglioma..........................................................................................................................3

Definitionofglioma................................................................................................................................5

Isgliomafrequent?.................................................................................................................................7

Whatcausesglioma?..............................................................................................................................8

Howisgliomadiagnosed?......................................................................................................................9

Whatisimportanttoknowtogetoptimaltreatment?........................................................................12

Whatarethetreatmentoptions?........................................................................................................14

Whatarethepossiblesideeffectsofthetreatments?........................................................................18

Whathappensafterthetreatment?....................................................................................................21

Definitionsofdifficultwords................................................................................................................24

ThistextwaswrittenbyDr.GiulioMetro(fortheAnticancerFund)andreviewedbyDr.GauthierBouche(ACF),Dr.SvetlanaJezdic (ESMO), Dr. George Pentheroudakis (ESMO), Prof. Roger Stupp (ESMO), Prof. Ulrich Keilholz (ESMO), HannekeZwinkelsRN,MAANP(EONS),OrejetaDiamantiRN(EONS),AnitaMarguliesBSNRN(EONS)andKathyOliver(InternationalBrainTumourAlliance).

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FACTSHEETABOUTGLIOMA

Definitionofglioma• Gliomas* are a group of tumours of the central nervous systemwhich differ according to the

cells of origin in the brain (astrocytes* or oligodendrocytes* or both) and the grade ofaggressiveness(fromtheleasttothemostaggressive:lowgradeglioma*!anaplasticglioma*!glioblastoma*).

Diagnosis• Glioma*canbesuspectedwhenanumberofsymptomsarepresent,suchasseizures*,changes

inpersonalityandbehaviour,varioustypesofneurologicalproblems(includingsightproblems,difficultyinspeaking,understandingwhatissaid,lossofstrengthorfeelinginapartofthebodyorgaitchanges),aswellassymptomsassociatedwithincreasedpressureinthehead(headache,nausea,vomiting,anddrowsiness).

• Magnetic Resonance Imaging (MRI*) of the brain is the gold standard radiological test for thedetectionofaglioma*.Italsohelpsdefinetheextentofthediseaseandindicateswhetherthetumourcanbesurgicallyremovedsafely.

• A piece of the tumour (taken either by surgical resection or by stereotactic*/open biopsy* incase surgical removal is not possible)must be obtained for analysis in the lab to confirm thediagnosis and getmore details about themolecular characteristics* of the tumour.Molecularcharacterisationmay help define the exact subtype of glioma*, gain information on the likelyoutcomeofthediagnosis(“prognosis”*)andhelpguidetreatmentdecisions.

TreatmentSurgeryisthefirsttreatmentofchoiceforthemajorityofnewlydiagnosedgliomas*;infact,surgicalremoval as extensive as safely possible is associatedwith an improved outcome regardless of thesubtypeofglioma*.Aftersurgery,treatmentdiffersaccordingtothesubtypeofglioma*.• Lowgradeglioma*(Grades1and2)

o Radiotherapy* is the standard post-operative treatment in patients whose diseasecharacteristicssuggestahighlikelihoodofreturnofthedisease(calledrecurrence*).

o Chemotherapy* has a less defined role in low grade glioma*. However, it can be used inpatients who are not deemed eligible for surgery and/or radiotherapy* or in tumoursrecurring after radiotherapy*. Patients whose tumour shows a specific molecularcharacteristic* (called ‘genetic loss on chromosomes 1p/19q’*) appear to be particularlysensitivetochemotherapy*,meaningthere ismorechanceofchemotherapeuticbenefit inthesepatients.

• Anaplasticglioma*(Grade3)o Radiotherapy* followed by chemotherapy* is a standard post-operative treatment in

anaplasticglioma*.o Radiotherapy* alonemay be used in anaplastic oligodendroglial tumours*without genetic

lossonchromosomes1p/19q*.

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o Studies have shown that chemotherapy* alone after surgery, and administeringradiotherapy* only at the time of disease progression, achieves the same results asradiotherapy*appliedaftersurgeryandchemotherapy*administeredatthetimeofdiseaseprogression.

• Glioblastoma*(Grade4)o Useofchemotherapy*andradiotherapy*incombination(‘concurrently’or‘concomittantly’)

is thestandardtreatmentaftersurgery inglioblastoma*patientsyoungerthan70yearsaswell as in older fit patients whose tumour tests positive for a specific molecularcharacteristic*(presenceofMGMTgenemethylation*).

o Radiotherapy*alone ispreferred inelderly (>70 years)patientswhoarenot fit enough toreceiveconcurrentchemo-radiotherapy*and/orwhosetumourisnegativeforthepresenceofMGMTgenemethylation*.

o Chemotherapy* alone is the preferred treatment option in elderly unfit patients whosetumourispositiveforMGMTgenemethylation*.

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DEFINITIONOFGLIOMAGliomas*representagroupofmalignancies*thatmayariseanywhereinthecentralnervoussystem,(‘CNS’)meaning in the brain or,much less frequently, in the spinal cord* (see illustration below).Theyarecharacterisedbyaninfiltrativepattern*ofgrowthand/oratendencyforspreadinglocallywithintheCNS.Tumourspreadtooutsidethebrainusuallydoesnotoccur.

Anatomyof thebrain, showing the cerebrum*, cerebellum*,brain stem*, andotherparts of thebrain. Theupperpartofthespinalcord*isalsorepresented.Following histopathological* examination, gliomas* are usually named according to the type ofnervouscellswhichtheyderivefrom(astrocytes*,oligodendrocytes*orependymalcells).Theclassificationofgliomas*followsascalefromItoIV(1to4),whichreflectstherateoftumourgrowth as well as its aggressiveness. Grade I tumours, which occur mainly in childhood, areassociated with the best prognosis*. Grade II (low grade gliomas*) represent slowly growing andinfiltrative tumours* with intermediate prognosis*. On the other hand, grade III (anaplastic) andgrade IV (glioblastoma*) tumours are both considered to be high grade gliomas*, as they areaggressiveandgenerallyhave the least favourableprognosis*.Thepresentguidewill focuson themanagement of low grade gliomas*, anaplastic gliomas* and glioblastoma*. The table belowprovidesanoverviewofthemaintypesofglioma*braintumoursaccordingtothecell theyderivefromandthegradetowhichtheybelong.

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*Ependymalcellsarea thirdtypeofglialcells.Raretumourscalledependymomas*(grade I to III)canarisefromthesecells.Informationonthetreatmentonthesetumoursisnotcoveredinthecurrentguide.** There are many subtypes of these tumours. They are classified and named according to their specificfeaturesunderthemicroscopeand/ortotheirlocationinthebrain.Forinstance,opticpathwaygliomas*arelow-gradegliomas*arisingfromastrocytes*locatingintheopticnerveorintheopticpathway.ImportantnoteregardingothertypesofbraintumoursSecondarybraintumours,alsocalledmetastases*tothebrainCancers that initially developed in other organs of the body (e.g. in the lung or the breast), canspreadtothebrain. Inthiscase,the‘secondary’tumourfoundinthebrainiscalledmetastasis*asopposed to a primary brain tumour developing initially in the brain. Themanagement of a brainmetastasis*isdifferentfromthemanagementofaprimarybraintumour.OthertypesofprimarybraintumourOther brain tumours also exist. Themost frequent other brain tumours aremeningiomas*whichdevelopfromthemeninges*andadenomas*ofthepituitarygland*whichdevelopfromcellsmakingthe pituitary gland*. Other types include ependymoma*, primitive neuroectodermal tumour andmedulloblastoma*whichareraretumoursarisingmainly inchildren.Themanagementofall thesetumoursisdifferentfromthemanagementofgliomas*andisthereforenotcoveredinthisguide.

Celloforigin* Nameoftumour** Grade CommentsAstrocyte* Astrocytoma* ItoIV GradesIandIIarecalledlowgradeastrocytomas*

GradesIIIandIVarecalledhighgradeastrocytomas*GradeIIIarealsocalledanaplasticastrocytomas*GradeIVarealsocalledglioblastomas*

Oligodendrocytes* Oligodendroglioma* II orIII

GradeIIarecalledlowgradeoligodendrogliomas*GradeIIIarecalledhighgradeoranaplasticoligodendrogliomas*

Mixed(astrocyte*andoligodendrocyte)

Oligoastrocytoma* II orIII

GradeIIarecalledlowgradeoligoastrocytomas*GradeIIIarecalledhighgradeoranaplasticoligoastrocytomas*

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ISGLIOMAFREQUENT?Glioma*isconsideredararecancerbecauseitaffectslessthan6outof100,000personseveryyear.Nevertheless, gliomas* represent 80%of all tumoursof the central nervous system.Gliomas* canaffect people of all ages including children, teenagers and young adults but aremore frequent inpeople intheir50sand60s.Worldwide,3womenand4menoutof100,000arediagnosedwithatumour affecting the central nervous system every year. In Europe, 5 women and 6 men out of100,000areaffectedeveryyear.Europehasthehighestratesperyear.WithinEurope,thehighestratesarereportedforSwedenandAlbania(10per100,000),andthelowestinCyprusandMoldova(lessthan4).On average, about one in every 150 European men and one in every 200 European women willdevelopatumourofthecentralnervoussystem(ofwhich80%willbemalignantglioma*),atsomepointintheirlife.

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WHATCAUSESGLIOMA?Beforeaddressingtheriskfactorsthatmaypredisposetothedevelopmentofglioma*,itisimportantto know that a risk factor increases the risk of cancer occurring, but is neither necessary norsufficienton itsowntocausecancer.A risk factor isnotacause in itself.Therefore,somepeoplewithoneormorerisk factorswillneverdevelopglioma*andsomepeoplewithoutanyof theseriskfactorsmaynonethelessdevelopglioma*.Nevertheless,atthepresenttime,itisnotclearwhyglioma*occurs,andveryfewriskfactorshavebeen identified.Generally speaking,gliomas*areslightlymorecommon inmen than inwomenaswellasinwhiteratherthanblackpopulations.Recognisedriskfactorsofgliomas*are:

• Ionisingradiation*Thisisanestablishedenvironmentalriskfactor,asdocumentedbythe observation that individuals exposed to atomic bombs andnuclear weapons testing have an increased risk of developingglioma*. Individuals who have received cranial irradiation* forcancer therapyduringtheirchildhoodarealsoat increasedriskofdevelopingglioma*yearsorevendecadeslater.

• FamilyhistoryA family history of glioma* (meaning oneormore cases of glioma* in the same family) isassociatedwitha2-foldincreaseintheriskofdevelopingaglioma*.

• GeneticsyndromesAnumberofrarehereditarysyndromesareassociatedwithahigherriskofdevelopmentofcancersingeneral,mainlyasaresultofthepresenceofoneormultiplegeneticalterations.Importantly, some of these hereditary syndromes may alsocarry a higher risk of glioma*, such as Cowden syndrome*,Turcot syndrome*, Lynch syndrome*, Li-Fraumenisyndrome*,andneurofibromatosistypeI*.

Other factors have been suspected to be associated with an increased risk of glioma*, but theevidenceisinconsistent.Thisisthecasewithcellphoneexposure,forwhichepidemiologicalstudies(researchintothepatterns,causesandeffectsofspecifichealthanddiseasepopulations)havefailedsofartoconclusivelydemonstrateanassociationwithanincreaseintheriskofglioma*.Evidenceisalsoinconsistentforotherfactorsoncesuspectedtoincreasetheriskofglioma*suchasheadinjury,aspartame,orexposuretopesticides.

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HOWISGLIOMADIAGNOSED?SignsandsymptomsGlioma* canbe suspected in thepresenceofdifferentsymptoms. Nevertheless, it is important to know thatthesesymptomslargelydependonthetypeofglioma*as well as on its exact location in the central nervoussystem. The different lobes of the left hemisphere ofthebrain are represented in the illustration. Thebrainhastwohemispheresandeachlobeineachhemisphereis responsible for a multitude of functions. Therefore,the list of symptoms reported herein cannot beexhaustive.However,inanefforttogeneralize,thefollowingsignsandsymptomsmaybecommonlypresenteitheraloneorcombinedwitheachotherbothatfirstdiagnosisorlateronduringthecourseofthedisease:

• Seizures*These are among the most common, and often most distressing, symptoms of gliomas*.Seizures*areespeciallypresent inpatientswithslowlygrowingtumourssuchas lowgradegliomas*.Aseizurecancausejerkingortwitchingofahand,armorleg.However,aseizuremay also affect the whole bodywith quite violent and uncontrolledmovements, possiblywith losing consciousness. A seizure can be a very frightening event so it is important forcarersorotherswitnessingaseizurenottopanic.Knowingwhattodowhenapersonhasaseizurecanreducefearandpotentialinjurytothepatient.

• Neurologicalproblems(knownas‘deficits’)Theselargelydependonthelobe(s)ofthebrainthatis(are)affected.Sightproblemsmaybepresent if the occipital lobe* (represented in blue) is involved. Difficulty in speaking orunderstandingwhatissaidtoyouaswellaslossoffunction(strength)orsensitivity(feeling)inapartofthebodyoccurswhenthefrontal(inyellow)orparietallobe(inred)isaffected.Personalityandbehaviouralchangessuchasapathy,lossofinitiative,andlossofemotionalcontrol/lossof inhibitionmayoccur if the frontal lobe*(inyellow) iscompromised.Finally,memorylossisoftenassociatedwithinvolvementofthetemporal(ingreen)lobe,whilepoorcoordinationoruncontrolledmovementof theeyes canbepresent if thedisease involvesthe‘littlebrain’ (cerebellum*).Whenglioma*arisesfromthespinalcord*,pain,numbnessand/or weakness in the lower part of the body, and/or loss of control of the bladder orbowelmaybepresent.

• SymptomsthatresultfromincreasedpressureinthebrainThesesymptomsaretypicalforhighgradegliomas*.Theyoccurbecausethetumourgrowsrapidly inthebrainwhich iscontained insidethefixedspaceoftheskull.Thiscanresult inheadache,nausea,vomiting,doublevisionanddrowsiness.

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• Thromboembolicevents*Thromboembolic events*,which are the formationof clots in theblood stream, are oftenpresent in glioma* patients. There are several possible reasons for this. Glioma* patientsoften carry risk factors commonly associatedwith thedevelopmentof thrombosis such asmotor deficits and/or immobility, and, after diagnosis, treatment with chemotherapy*.Symptomsassociatedwiththrombosislargelydifferaccordingtotheinvolvedsite,andtheirlistisbeyondthescopeofthisguideforpatients.

Clinicalexamination*Testing the central nervous system is the most important part of the clinical examination* if aglioma* is suspected or diagnosed. However, general physical examination (e.g. breast, abdomen,skin) isalsoimportantsothatsignsofacancersomewhereelseinthebodycanbeexcluded.Withregardtoneurologicalexamination*,thephysicianmayaskafewquestions,aswellasperformsomesimpletests.Neurologicalexamination*usuallyincludes:

• Testing your strength by asking you to squeeze the physician’s hands or push against thephysician’shandwithyourfeet.

• Checkingtoseethatyouhavenormalsensationthroughoutthebody• Askingyoutotouchyournosewithyourfingerwhileyoureyesareshut• Askingyoutowalkinastraightline• Askingyoutoanswersimplequestions• Askingyoutofollowamovingfingerwithyoureyes• Askingyouaboutyourhearingandsight

Radiologicalexamination*Radiologicaltestsarecrucialexaminationswhichdetectaglioma*anddefineitsexactlocationandextent.Asglioma*doesnotmetastasisetodistantorgans,diagnosticimagingislimitedtothebrain.

• CT-scan*ofthebrainThis radiological test is often the first exam to beperformed when a brain tumour is suspected. That isbecauseabraintumourusuallyshowsuponthistypeofscan. The injection of contrast-medium, namely a dyethat circulates in your bloodstream, before this testallows for a clearer picture of the brain. It is veryimportant to tell your doctor if you have had previousallergicreactionstothiscontrast-medium.

• MRI*ofthebrainMRI* is the gold standard examination for the radiological diagnosis* of glioma*. AscomparedtoCT-scan*,MRI*givesamuchclearerpictureofthebrain.SimilarlytoCT-scan*,MRI* is performed following the injection of contrastmedium. It is very important to tellyourdoctorifyouhavemetalinsideyourbodyasthismaymeanyoucannothaveanMRI*scan.

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Histopathologicalexamination*This is the laboratory examination of the tumour cells. It can beperformed either on the tumour(s) removed by surgery or onbiopsies* coming from stereotactic procedures* (see treatmentoptions) of surgically inoperable gliomas*. Importantly,histopathological examination* is the only method that candefinitively confirm a diagnosis of glioma*. In general, themoretumour tissue is available, the more accurate the diagnosis is.However, histopathological examination* can yieldmore preciseresults when carried out at experienced centres wherepathologists* (the medical specialists who examine your tissueafterithasbeenremoved)haveparticularexperienceofanalysingbraintumours.Therefore,carefulreviewoftumourcellsbyanexpertneuropathologist*iscrucial.

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WHATISIMPORTANTTOKNOWTOGETOPTIMALTREATMENT?Doctorswillneedtoconsidermanyaspectsaboutyouasthepatientandyourtypeofbraintumourinordertodecideonthebesttreatment.Relevantinformationaboutyou

• Yourage• Yourperformancestatus*,namelyameasurementscaleofyourgeneralconditionthatis

influencedbythepresenceandseverityoftumour-relatedsymptoms• Yourpersonalandfamilymedicalhistory,includingtypeandnumberofotherdiseases• Resultsofyourbloodtests(e.g.whitebloodcells*,redbloodcells*,platelets*count,liver

andkidneyfunction).Relevantinformationaboutyourbraintumour

• Histopathologicalexamination*Histopathological examination* of gliomas* is the basis for guiding optimal treatment. Ingeneral, gliomas* can be classified according to grade into low grade gliomas*, anaplasticgliomas*andglioblastoma*. Inaddition, lowgradeandanaplastic gliomas*canbe furtherclassified according to the type of cells they derive from, namely astrocytes*,oligodendrocytes*, or both. It should be noted that ependymomas*, which are gliomas*derivingfromependymalcells,alsoexistbuttreatmentofependymomas*isnotcoveredinthecurrentguide.This classification results in different treatment approaches as well as a different overallprognosis*,normallybasedonstatistics.Statisticsareatoolusedforcomparingtreatmentsandfordescribingwhathashappenedinthepasttogroupsofpeoplewithvarioustumourtypes. Statistics cannot predict exactly how long any individual personwill live sopatientsshouldnotnecessarilyconsiderstatisticsasacompletelyaccurateindicatoroftheirlifespanafterdiagnosis. Individualprognosis* isbestdiscussed,ona caseby casebasis,withbraintumourspecialists.Inordertoprovideageneralideaonprognosis*,weknowfromstatisticsthatingeneralthelowerthegradeofthetumour,thebettertheprognosis*.Butthereareexceptionstothesestatisticsandthereareevensomeverylongtermsurvivorsofanaplasticastrocytoma*andglioblastoma*.

o GradeIIoligodendrogliomas*o Anaplasticoligodendrogliomas*(alsocalledgradeIII)o GradeIIastrocytomas*o Anaplasticastrocytomas*(alsocalledgradeIII)o Glioblastomas*(alsocalledgradeIV)

In addition to grade and subtypes, other established prognostic factors include your age,yourperformancestatus*,thepossibilityofresectionofthetumour,yourgeneralconditionandyourcognitivefunction(aperson’smentalabilitiesandprocesses).Therecentadvancesin discovery of tumour markers (as explained below) have made it possible to predict apotentiallybetteroutcomeformalignantglioma*withspecifictumourcharacteristics.

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• Molecularmarkers*ofthetumourThefollowingmarkershavetobetakenintoaccountforanalysisbyyourphysicianbecausetheycaneitherprovideinformationontheprognosis*ofthetumourorhelpguidetreatmentdecisions.

o Geneticlossonchromosomes1p/19q*The detection of this marker is important in order to ascertain the diagnosis ofglioma* with an oligodendroglial component (either pure oligodendroglioma* ormixedoligoastrocytoma*).Also,itidentifiesatumourentitywithaslowercourseofdisease, and which shows particular sensitivity both to radiotherapy* andchemotherapy*.

o MutationoftheIDH*gene1or2Amutationinthisgeneisoftenpresentbothinlowgradeandanaplasticgliomas*,whereitisassociatedwithabettersurvivalregardlessoftreatment.Itspresenceinhigh grade gliomas* (anaplastic gliomas* or glioblastoma*) suggests that thesetumours developed from a previously low grade glioma*. Therefore, high gradetumours with a mutation in the IDH* gene generally have a better prognosis*comparedwithhighgradegliomas*withoutIDH*mutation.

o MGMT*genemethylationThepresenceofthismarkerreflectstheinabilityofthetumourtorepairthedamageon the DNA produced by certain chemotherapies called ‘alkylating agents’*,particularly temozolomide*. Therefore, when this alteration is found inglioblastoma* it suggests the tumour is more sensitive to temozolomide* (seetreatmentoptions).

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WHATARETHETREATMENTOPTIONS?SurgeryRegardless of the glioma* subtype, surgery (either surgical resection orstereotactic*/open biopsy*) represents an essential component oftreatmentofallnewlydiagnosedgliomas*.

• SurgicalresectionSurgicalresectionofthetumouristhepreferredinitialtreatmentforthe majority of gliomas*. Surgery is aimed to be as complete aspossible. The reason for this is thatmaximal tumour resectionhasbeenshowntoresultinlongersurvivalandallowformoreeffectivepost-operativetherapiestobegiven.But ifsuchradicalsurgery* isexpectedtoimpairneurologicalfunction,itshouldbeaimedjustatremovingasmuchtumourasissafelypossible,sparinghealthytissues.Inaddition,surgicalremovalofthetumourprovidesasufficientamountoftissueforbothanaccuratehistopathologicaldiagnosis*andmolecularcharacterisationofthetumour.

• Stereotactic*/openbiopsy*If surgery is not safely feasible,mainly due to tumour location (e.g. surgically inaccessibleregionoraregionthatcarriesahighriskforsignificantimpairmentofneurologicalfunction)or due to a deteriorated clinical condition, a stereotactic* or open biopsy* may beconsideredtoobtaintissueforadiagnosis.Abiopsy isnotatreatmentforthetumourbutanalysis of the tissue removed by biopsy will allow for planning the best treatment. Astereotacticbiopsy*isalessinvasivewaytoobtainthetissuesample,whileanopenbiopsy*is surgery that uses local or general anesthesia to remove the tissue needed for thediagnosis.Inexperiencedhands,astereotacticbiopsy*providessufficienttissueforacorrecthistopathological diagnosis* in more than 95% of cases. However, in order to provide asmuch tumour tissue as possible for both diagnosis and molecular characterisation, openbiopsy*,maybepreferred.

Radiotherapy*and/orchemotherapy*Post-operative treatments mainly consist of chemotherapy* and/orradiotherapy*. However, their use differs according to the subtype ofglioma*.

• Lowgradeglioma*(WHOgradeIandgradeII)Lowgradegliomas*comprisethehistologicaltypesofastrocytoma*,oligodendroglioma*andoligoastrocytoma*1.

1Lowgradeependymomas*arealsolowgradegliomas*.However,treatmentofependymomas*differsfromtreatmentofothergliomas*andisthereforenotcoveredinthecurrentguide.

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o Radiotherapy*Post-operativeradiotherapy*isthestandardtreatmentforlowgradegliomas*.Itisusuallyadministeredin28sessionsover6weeks.Nevertheless,notallpatientswhoundergo resection of a low grade glioma* should be treated with radiotherapy*.That isbecause thesepatientsmayhavea longer/slowernaturalhistoryofdiseaseevenintheabsenceofpost-operativetreatment.However,post-operativeradiotherapy*shouldalwaysbeconsideredinthepresenceofthreeormoreofthefollowingfactorswhichsuggestahigherlikelihoodoftumourrecurrence*:

• tumoursgreaterthan5cmindiameter,• age>40years,• absence of an oligodendroglial component at histopathological

examination*,• tumoursextendingfromonebrainhemispheretotheother,• presenceofneurologicaldeficitsbeforesurgery.

o Chemotherapy*Temozolomide*chemotherapy*givenorally is thepreferred treatment option for patients who arenot deemed eligible for surgical resection and/orradiotherapy* because of tumour location andtumour dimension/appearance at MRI*,respectively. Also, temozolomide* can be usedif/when disease recurs following radiotherapy*.There is some evidence suggesting that tumourswithgenetic losson chromosomes1p/19q*mightbemore sensitive to chemotherapy* as compared to low grade gliomas*withoutthisalteration.

• Anaplasticglioma*(WHOgradeIII)Similarly to low grade gliomas*, anaplastic gliomas*comprise the histological types of astrocytoma*,oligodendroglioma* and oligoastrocytoma*. However,they differ from low grade glioma* because of somehistological and/or radiological characteristics whichsuggestamoreaggressivebehaviourofthetumour.

o Radiotherapy*Post-operative radiotherapy* is the standardtreatment for anaplastic astrocytoma*. It isusuallyadministeredin33sessionsover6.5weeks.Radiotherapy*alonemayalsobeconsidered for anaplastic oligodendroglioma* and oligoastrocytoma* withoutgenetic loss on chromosomes 1p/19q*. On the other hand, radiotherapy* giveneither before or after chemotherapy* should be considered for anaplasticoligodendroglioma* and oligoastrocytoma* with genetic loss on chromosomes1p/19q*.

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o Chemotherapy*Post-operative chemotherapy* of the orally administered chemotherapeutic agenttemozolomide* or the three-drug chemotherapy* regimen called PCV*(procarbazine*, lomustine*andvincristine*)shouldbeconsideredasanalternativeto radiotherapy* for anaplastic gliomas*. Between the two regimens,temozolomide* is usually preferred because of its greater tolerability and ease ofadministration. Genetic loss on chromosomes 1p/19q* identifies the anaplastictumours with an oligodendroglial component* which are more sensitive tochemotherapy*withorwithoutradiotherapy*.

• Glioblastoma*(WHOgradeIV)Post-operative treatment of glioblastoma* may differ according to some of yourcharacteristics (i.e. age, performance status*) and histopathological/molecular features ofyourtumour(i.e.MGMT*statusofthetumour)

o Concurrentchemo-radiotherapy*The concurrent administration of chemotherapy* during radiotherapy* and thenchemotherapy*on itsownforaperiodof timeafterradiotherapy* is thestandardpost-operativetreatmentofpatientswithglioblastoma*upto70yearsofage; it isalso the preferred treatment approach for fit elderly patients older than 70 yearswhosetumourhastestedpositiveforthepresenceofMGMTgenemethylation*.

" Chemotherapy* consists of the orally administered drug calledtemozolomide*, which acts by interfering with the mechanism of DNAreplication of cancer cells. Temozolomide* is administered daily from thefirst day of radiotherapy* and for the whole duration of it. At the end ofradiation, after a short treatment break (approximately 4 weeks),temozolomide* is resumed at a higher dosage for at least 6 cycles (sixmonths) of therapy. Although the addition of temozolomide* toradiotherapy* is beneficial for most of patients with glioblastoma, it isimportant to know that the greatest benefit is observed inpatientswhosetumourisdetectedpositiveforMGMTgenemethylation*testing.

" Radiotherapy*isadministeredconcurrentlywithtemozolomide*for5daysaweekforatotalof6weeks,i.e.in30separatesessions.

o Radiotherapy*Elderly patients older than 70 years who are not deemed eligible for concurrentchemo-radiotherapy*becauseofdeterioratedperformancestatus*and/orbecausetheirtumourhastestednegativeforthepresenceofMGMTgenemethylation*,areadequatelytreatedwithradiotherapy*aloneusingahypo-fractionatedschedule.Ahypo-fractioned schedule* consists of administering higher daily doses ofradiotherapy*overashorterperiodoftime.Hypo-fractionatedradiotherapy*aloneis also appropriate for elderly patients inwhomno information is availableon theMGMT*status.

o Chemotherapy*aloneElderly patients older than 70 years who are not deemed eligible for concurrentchemo-radiotherapy*, may be adequately treated with temozolomide*chemotherapy*, provided their tumour has tested positive for the presence ofMGMTgenemethylation*.

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Medicationstorelievesymptomsofaglioma*Thesymptomsandsignsmentionedinthesectionaboutdiagnosiscanimproveorevendisappearifeffective therapiesareused to treatglioma*successfully (seeaforementioned treatmentoptions).However,thefollowingmedicationsareusedinordertoeffectivelycontrol,atleastinpart,tumoursymptoms:

• Anti-epilepticdrugsAnti-epileptic drugs are very effective medications for patients who have seizures*.However, these drugs should not be used for the prevention of seizures* in patientswhohavenever experiencedone. There are several typesof anti-epileptic drugs.Nevertheless,only a few anti-epileptic drugs (lamotrigine*, levetiracetam*, pregabalin*, or topiramate*)offertheadvantageoflackofinterferencewiththecommonlyprescribedchemotherapeuticagents*. Notwithstanding, clinical studies have demonstrated that temozolomide* can besafelyadministeredwithanytypeofanti-epilepticdrug.

• Corticosteroids*Corticosteroids* alleviatepatients’ symptomsby reducing tumour-associated inflammation(called‘oedema’*),whichusuallyformsaroundthetumourandcontributestosymptomsbyincreasing intracranial pressure. Therefore, corticosteroids* are indicated if oedema* isdetected at radiological tests, or if the responsible physician decides on startingcorticosteroid* treatmentbasedonsignsandsymptomsof increased intracranialpressure.Unfortunately,thedownsideofcorticosteroids*isthattheirlong-termusecanbeassociatedwithsomesideeffects(e.g.Cushingoidormoonface,conditioninwhichfataccumulatestothesidesoftheface,givingitaroundedappearance,also increaseinbloodglucoselevels*whichthereforeshouldbemonitoredateachvisit,increasedriskofinfection,osteoporosis,muscle weakness, impaired wound healing). For this reason, upon improvement ofsymptoms, the dose of corticosteroids* should be gradually reduced in order to find thelowest effective dose or eventually be discontinued if symptoms resolve and/or oedema*disappearsasaresultofeffectivetreatmentofthetumour.

• Anticoagulation*Anticoagulation*usingcoumadinderivatives*(i.e.warfarin*) isfeasible inglioma*patientsexperiencing thromboembolic events*; however, low-molecular-weight heparin* is oftenpreferredduetoafavourablesafetyprofile.

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WHATARETHEPOSSIBLESIDEEFFECTSOFTHETREATMENTS?In this section you can find the most common side effects of surgery, radiotherapy* andchemotherapy*.However,thefollowinglistisnotexhaustive.Therefore,youshouldcarefullydiscusswithyourdoctorthesideeffectspotentiallyrelatedtotheproposedtreatment(s).Surgery

• EpilepsySomepeoplewillhaveseizures*withinthefirstweekofsurgery,butthisdoesn’tmeanthatsurgery has not been successful. Seizures* after surgerycan happen because of the directstress thebrainexperiencesduring the surgicalprocedure.On theotherhand, if seizures*wereoneofthesymptomsofdiseasepresentation,aftersurgerytheywilllikelyimproveorevendisappearovertime.However, itmaytaketimetofullymeasurehowsuccessfulyoursurgeryhasbeenintermsofseizureimprovement.

• BleedingThereisapossibilityofpost-operativeintracranialbleedingincaseswhensurgicalremovalofa glioma* has been carried out. This bleeding causes an increase in intracranial pressure.However, only rarely this increase in pressure eitherwithin or on the brain aswell as thesurrounding structures has the potential to reach alarmingly high levels, thus leading toeitherunconsciousnessorotherseriouscomplications.

• NeurologicaldeficitsIf present at diagnosis, neurological deficits usually improve following surgery. However,surgical removal of tumour tissue in the brain sometimes leads to removal of healthyunaffectedbraintissueaswell,thuspotentiallycausingneurologicaldeficits.Theymayvaryin type and severity, and can be either temporary or permanent. Symptoms graduallydisappear in temporary caseswithinmonths, butwhere permanent damage of tissue hasoccurredrehabilitationmaybe required. Insomecases,brain tissuedamagecanalsoalterpersonalityorcausechangesinmood.

• InfectionsTogainaccesstothebraintumour,apieceoftheskullistemporaryremovedfromitsplace,under sterile conditions. Nevertheless, bacteria may gain access to the brain during theoperatingprocedure,andthenthechancesofbraininfectionarehigh.Topreventthistypeof infection, an intravenously* administered antibiotic is given to the patient during theoperatingprocedure.Asacut ismadeontheskinandahole ismade in theskull, there isalways the possibility of an acquired skin or skull infection. A proper antibiotic regimen isstartedimmediatelyinsuchcasestotreattheinfection.

• Cerebrospinalfluidleak*(alsoknownasa‘CSFleak’)Surgeryofthebraincancausealeakofthecerebrospinalfluid,afluidproducedbythebrain.Headache,asaltytaste inthethroatorawaterydrainagefromthenose(usuallyfromonenostril)orfromthewoundsitearethemostcommonsymptoms.However,acerebrospinalfluid leak* may also give no symptom. A cerebrospinal fluid leak* needs to be rapidlyrepairedsinceitincreasestheriskofbacterialinfectioninthebrain(meningitis*orabscess).

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Radiotherapy*• Sideeffectswithanearlyonset

Sideeffectsusuallyoccurduringorwithin6monthsaftercompletionofradiotherapy*.Theyoften include nausea/vomiting, headache, aworsening of the existing neurological deficits(due to radiotherapy* induced swelling, which is called ‘oedema’*) and hair loss in theirradiatedareaaswellasontheoppositesideoftheheadwheretheradiotherapy*beamspass through. In glioma* patients, radiotherapy* can also cause an increase in the risk ofseizures*asoneofthebrain’sreactionstothistreatment.

• SideeffectswithalateonsetThesesideeffectstypicallyoccur6monthsormorefromcompletionofradiotherapy*.Themost common ones include radio-necrosis* (meaning death of healthy brain tissue in thepreviouslyirradiatedarea)which,insomeinstances,mayleadtosymptomsassociatedwithincreasedpressureinthehead(i.e.headache,nausea,anddrowsiness),and/orneurologicaldeficits. Late side effects may also include partial loss of short-term memory, whoseoccurrencestrictlydependsontheareaofthebrainwhichhasbeenirradiated(i.e.temporallobe*).

Chemotherapy*Thesideeffectsofchemotherapy*varyinfrequencyandseveritybasedonthetypeofagentand/orcombinationregimensemployed.Therefore,youareencouragedtothoroughlydiscussthemainsideeffectsassociatedwiththeproposedchemotherapy*regimenwithyourdoctor.However, ingeneral,commonsideeffectsofchemotherapy*mayinclude:lossofappetite,fatigue,hairloss,nauseaand/orvomiting,increasedsusceptibilitytoinfectionsandbleeding.Nevertheless,itisimportanttonotethatnoteveryonewillhavesideeffects,orexperiencethemtothesameextent.Here,youcanfindsomespecificsideeffectsofthemostcommonlyadministeredchemotherapeuticagents*forthetreatmentofgliomas*.

• Temozolomide*This orally administered chemotherapeutic agentmay cause a reduction in the number ofplatelets* as one of itsmost common side effects. Platelets* are cellular elements of thebloodwhosefunctionistohelpstopbleeding.Asaconsequence,theriskofbleedingmaybeincreasedduringchemotherapy*with temozolomide*.This is the reasonwhy the levelsofplatelets*shouldbemonitoredandevaluatedcarefullyatthebeginningandduringtherapywithtemozolomide*.Nausea and/or vomiting areother common side effects of temozolomide*.However, theycanbelargelypreventedwiththeuseofanti-emetic(anti-nausea/anti-vomiting)drugstobeadministeredbeforetakingtemozolomide*.Finally,pneumoniadue toopportunisticpathogens* is a rare sideeffectof temozolomide.Temozolomide* can weaken the immune system by lowering the level of lymphocytes, asubtype of white blood cells*. Thismay result in a life-threatening pneumonia caused bymicrobes*thatonlyaffectimmuno-compromisedpatients.

• Procarbazine*,lomustine*andvincristine*(‘PCV’*)Thesedrugsareusuallyadministeredincombination(oraladministrationforprocarbazine*andlomustine*,andintravenousadministrationforvincristine*).

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Procarbazine*and lomustine*canoften lead toa reduction in thenumberofwhitebloodcells*,whichareelementsofthebloodinvolvedinprotectingthebodyfrominfections.Thenumberofplatelets*mightalsodecrease.Thisiswhythebloodcountsshouldbemonitoredandevaluatedcarefullyatthebeginningandduringtherapywithprocarbazine*,lomustine*andvincristine*.Vincristine*cancauseperipheralneuropathy*,whichisaprogressiveandoftenirreversibletingling,numbnessandpaininthehandsandfeet.Thesesideeffectsmayhaveanimpactontheactivitiesofdailylivingandmustimmediatelybereportedtotheresponsiblephysician.Itmay lead to a dose reduction or interruption of vincristine*, as the best interests of thepatientareforemostinanytreatmentplan.Nauseaand/orvomitingareanothercommonsideeffectoflomustine*.However,theycanbelargelypreventedwiththeuseofanti-emeticdrugstakenrightbeforelomustine*.

Shouldyouconsiderclinicaltrials?Theprognosis*forpatientsdiagnosedwithgliomas*isverydifferentfromonetumourtoanotherInallcases,butespeciallywhentheprognosis*islessfavourable,clinicaltrials*shouldbeconsidered.Inmanycountries,clinicaltrialsmaybeavailablefornewlydiagnosedpatientsaswellasforpatientswhoalreadyreceivedstandard, first-line treatmentandwhomaybedealingwitha recurrence*oftheirdisease.Asthereisstillunmetneedforimprovingtheeffectivenessoftreatmentsforgliomas*,doctors and scientists are exploring new therapies. For instance, immunotherapies, newneurosurgical techniques, newmethods of irradiation*, newdevices and targetted therapies haveshownpromiseandareallbeingtestedinclinicaltrialsinsomecountries.Promising therapies have to first be tested stringently in clinical trials before they are approved(licensedforaspecificuse)byregulatorybodiesandthenmadeavailabletopatients.Theseclinicaltrialsmayprovideanopportunity to receiveanewtherapybefore it isgenerallyavailable.On theotherhand,suchnewtherapieswhichareused in researchstudiesalsohavesomerisksas,at theclinicaltrialstage,allofthesideeffectsarenotyetknown.Becauseofthesepositiveandnegativeaspectsof clinical trials, it is very important thatyou thoroughlydiscuss the suitabilityofa clinicaltrialwithyourdoctor.Mostoftheclinicaltrialsforgliomas*arelistedonthefollowingwebsites:

• https://www.clinicaltrials.gov/ct2/results?cond=%22Glioma%22• https://www.clinicaltrialsregister.eu/ctr-search/search?query=glioma

More information onwhat clinical trials are andwhat it takes to participate can be found on thefollowingwebsite:http://www.anticancerfund.org/what-is-a-clinical-trial-0

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WHATHAPPENSAFTERTHETREATMENT?EvaluatingyourresponsetotreatmentMRI*isthepreferredimagingmethodforassessingtreatment(s).YourfirstMRI*shouldbecarriedoutwithin24-48hoursaftersurgery. It is inordertoverifythetrueextentoftumourresection,todetect the presence of any residual disease* and to look for any bleeding. The intervals ofsubsequent MRI* assessments may vary depending on the type of glioma*, on how it is beingtreated,andonthesymptomsyoureport.Generally speaking, the results of the MRI* scan should always be viewed in relation to theneurologicalstatus*ofthepatientandtheuseofcorticosteroid*therapy.As for glioblastoma* treatedwith concurrent chemo-radiotherapy* a firstMRI*will preferably beperformed3to4monthsaftertheendofradiotherapy*,after2or3adjuvanttemozolomide*cycles.AnMRI*performedwithin4-12weeksaftertheendoftreatment,maybedifficulttointerpretdueto reactive changes in the tumour, and a possible falseMRI* reading of disease progression (thisphenomenon is called ‘pseudoprogression’*). A repeatedMRI* after 6-8weeks,will help evaluatethis phenomenonanddisclosewhether there is trueprogressionor not. It is important todiscussMRI* findings and neurological condition* of the patient in a multidisciplinary tumour board, todecideoncontinuationofthetreatment.Follow-upwithyourdoctorsRegularfollow-upwithyourdoctorsisimportantinordertoevaluateneurologicalfunction,seizure(s)andcorticosteroid*use. Corticosteroids* should be tapered off as soon aspossible in view of their long-term use side effects.Laboratory tests may help find out complications ofsymptomatic medication(s)*, as corticosteroids* mayincreasebloodglucose levels*,andanti-epilepticdrugsmayalterbloodcellcountandliverfunctiontests.Duringfollow-up, MRI* should be performed every 3-4 months, unlessearlierormorefrequentmonitoringisclinicallyindicated.ReturningtonormallifeReturning to normal life can be difficult for glioma* patients, as different degrees of neurologicalimpairment may be present. Patients become increasingly less independent as a result of directinjuryofbrainstructuresresponsibleformotor,sensory,cognitive,andspeechfunctions.Also, theindirect effects of radiotherapy* and chemotherapy* may add to the functional deficit whichpatientsexperience.For these reasons, rehabilitation isofcrucial importance forglioma*patients,and emphasis should be placed on restoring or maximising independence with activities of dailyliving,mobility,cognition*andcommunication.However, though rehabilitation interventions can be applied in all stages of the disease, its goalschange as the stage of illness advances.When tumour progression causes a decline in functionalskills, rehabilitation assumes a supportive role, with goals adjusted to accommodate persistentphysical and functional limitations. During advanced stages of illness, palliative rehabilitation canimproveandmaintaincomfortandqualityoflife.

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Psychological,socialandpeersupportPsychologicalstressandthesocialeffectsofthediseaseonpatientsandtheirfamiliesandcaregiversshould not be underestimated. Psychiatric difficulties should be recognised and treatedwith bothpsychotherapyandpharmacotherapy.Recognitionofthesocialeffectsofhavingabraintumourandadequatecounsellinginsuchcircumstancesarevitalaspectsofcareforpatientsandtheircaregivers.A dedicated nurse in a neuro-oncology centre can be responsible for guiding and supporting thepatient as well as the caregiver during the disease journey. Referral to other health careprofessionals suchaspsychologists, socialworkers,physiotherapistsand speechpathologists*mayhelpthepatientandcaregiveralleviatetheexperiencedburdenandmeettheirneeds.Patientadvocacygroups* canhelp youget in touch with other patients whohave brain tumours, assist you inlearning more about your disease,provide helpful information, find anexperienced doctor for a secondopinion, identify clinical centers ofexpertise that run clinical trials* andprovide other services to help you andyourfamilydealwiththediagnosisofabrain tumoursoyoudonot feelalone.Toseewhetherabrain tumourpatientorganisationexists inyourcountry,youcan visit the website of theInternational Brain Tumour Alliance athttp://theibta.org/brain-tumour-support-advocacy-and-information-organisations/Whatifmygliomacomesback?The treatment at disease recurrence* differs according to the type of initial histopathologicaldiagnosis*andclinicalscenario,typeandnumberofprevioustherapies.Treatmentoptionsinclude:

• Chemotherapy* in patients with good performance status* who have not received prioradjuvantchemotherapy*,

• secondsurgery(inparticularifaperiodoftimehaselapsedsincefirstsurgicalresection,orwhenrecurrenttumourcausessymptomsduetoitsmasseffects),

• (re)-irradiation*(incaseofsmallertumours).Forpatientsprogressingafterpriorchemotherapy*,thereis,asyet,nospecificprotocolestablishedfor a second chemotherapy* regimen or targeted agents* and therefore, patients should beencouragedtoparticipateinclinicaltrials*,iftheyareavailable(seeparagraph“Shouldyouconsiderclinical trials?” in the section “What are the treatment options?”). Chemotherapy* with a PCVregimen* or a single agent nitrosourea*may achieve similar tumour control rates comparedwithtemozolomide*.However, it should be noted that there is no agreed standard therapy when disease recurs, andclinical decision making should ideally be based on recommendations from a multidisciplinarytumourboardwhowillreviewyourcase.

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SupportiveandpalliativecareMedicationstorelievesymptomsexperiencedbypatientswithglioma*areaveryimportantpartofcare as already explained. However, during and after the course of active anticancer treatment,some side effects can occur and adequate supportive measures should be applied (such as anti-emetic therapy, corticosteroids*, antibiotic therapy,blood transfusion, etc.dependingon the typeand severity of underlying side effects). This is known as supportive and palliative care. It isimportantforpatientsandcarerstorememberthattheterm‘palliativecare’doesnotonlyapplytoend-of-lifecarebutitappliestorelievingsymptomsatanystageofdisease,includingwhenyouarenewlydiagnosed.Soyoushouldnotbefrightenedwhenyouhearthewords‘palliativecare’.In summary,and importantly,being informedabout theavailable therapies forabrain tumourwillhelpyoutobemoreactivelyinvolvedinthedecisionsregardingyourtreatment.Notonlythat,butitcan also open up the possibility of more in-depth discussions with your medical team as manyquestionsmayarise.Do not hesitate to ask questions and to give your opinion. You, as the patient, are the primaryconcernandeverybodyistheretohelpyou.

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DEFINITIONSOFDIFFICULTWORDSAdenomaBenigntumourofglandularorigin.Overtimethisbenigngrowthmaybecomemalignant,andevenwhilebenignitcanhavehealthconsequencesbycompressingotherstructuresorbyproducinglargeamountsofhormones.AlkalytingagentAtypeofdrugthatisusedinthetreatmentofcancer.ItinterfereswithDNAandinhibitscellgrowth.AnaplasticgliomaBraintumourcharacterisedbycellsthatdividerapidlyandhavelittleornoresemblancetonormalcell.AnaplasticoligodendroglialtumoursType of brain tumour or glioma characterised by cells that divide rapidly and have little or noresemblancetonormalcells.AnticoagulationPrevention of blood clotting bymeans of anticoagulant drugs. Anticoagulant drugs are also calledbloodthinners.AstrocyteA large, star-shapedcell thatholdsnervecells inplaceandhelps themdevelopandwork thewaytheyshould.Anastrocyteisatypeofglialcells.AstrocytomaAtumourthatbeginsinthebrainorspinalcord*insmall,star-shapedcellscalledastrocytes*.BloodglucoselevelsGlucose(atypeofsugar)foundintheblood.Alsocalledglycaemia.BrainstemThepartofthebrainthatisconnectedtothespinalcord*.CerebellumTheportionofthebraininthebackoftheheadbetweenthecerebrum*andthebrainstem*.Thecerebellum controls balance for walking and standing, and other complex motor functions. (Seepictureinpage24).CerebrospinalfluidleakEscapeofthefluidthatsurroundsandbathesthespinalcord*andbrain.Themainfunctionofthisfluidistoprotectthebrainandthespinalcord*.

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Anatomy of the inside of the brain, showing the pineal and pituitary glands*, optic nerve, ventricles (withcerebrospinalfluidshowninblue),andotherpartsofthebrain.CerebrumThe largest part of the brain. It is divided into two hemispheres, or halves, called the cerebralhemispheres.Areaswithinthecerebrumcontrolmusclefunctionsandalsocontrolspeech,thought,emotions,reading,writing,andlearning(Seepictureinpage24).Chemo-radiotherapyTreatmentthatcombineschemotherapy*withradiotherapy*.Alsocalledchemoradiation.Chemotherapy/ChemotherapeuticagentsAtypeofcancertreatmentusingdrugsthatkillcancercellsand/or limit theirgrowth.Thesedrugsare usually administered to the patient by slow infusion into a vein but can also be administeredorallyviaatabletorcapsule.ClinicalexaminationTheexaminationofthebodytosearchforsignsofdisease.CognitionThescientifictermfortheprocessofthought.Corticosteroid(therapy)Corticosteroidsaresteroidhormonesmadeintheouterpartoftheadrenalglands.Theycanalsobesynthetically produced in the laboratory, as they are used for therapeutic purposes.Theymay beusedashormone replacement, to suppress the immune system,and to treat some sideeffectsofcancer and its treatment. Corticosteroids are also used to treat certain lymphomas and lymphoidleukaemias.Inbraintumourstheyareusedtorelievethebrain’sswelling(oedema*)causedbythepresenceofthetumour.

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CoumadinderivatesCoumadin,alsocalledwarfarin*,isadrugthatpreventsbloodfromclotting.Itbelongstothefamilyofdrugscalledanticoagulants.CowdensyndromeAninheriteddisordermarkedbytheformationofmanynoncancerousgrowthscalledhamartomas.Thesegrowthsoccurintheskin,breast,thyroid,colon,intestines,andinsideofthemouth.PatientswithCowdensyndromeareatincreasedriskofcertaintypesofcancer,includingbreastandthyroid.AlsocalledCowdendiseaseandmultiplehamartomasyndrome.CT-scanAformofradiographyinwhichbodyorgansarescannedwithX-raysandtheresultsaresynthesizedbyacomputertogenerateimagesofpartsofthebody.EpendymomaA type of brain tumour that begins in cells lining the spinal cord* central canal (fluid-filled spacedownthecentre)ortheventricles(fluid-filledspacesofthebrain).Ependymomasmayalsoforminthe choroid plexus (tissue in the ventricles thatmakes cerebrospinal fluid). Also called ependymaltumour.FrontallobePart of the brain located in the frontal upper part of the brain. It is responsible for mentalprocessessuchasthinking,decisionmaking,andplanning.Thefrontal lobealsoplaysan importantpartinretaininglongertermmemorieswhicharenottask-based.Geneticlossonchromosome1p/19qGenetic mutation that is associated with a type of brain tumour called oligodendroglioma*. Thismutationisusedasapredictorofresponsetochemotherapy*andsurvival.GlioblastomaAfast-growingtypeofcentralnervoussystemtumourthatformsfromglial(supportive)tissueofthebrainandspinalcord*andhascellsthatlookverydifferentfromnormalcells.Glioblastomausuallyoccurs in adults and affects the brain more often than the spinal cord*. Also called grade IVastrocytoma*.GliomaAcancerofthebrainthatbeginsinglialcells(cellsthatsurroundandsupportnervecells)HighgradegliomaTheyaretumoursthatoriginateinthebrain.Asopposedto lowgradetumourshighgradegliomasgrowfastandhave the tendency to infiltrateadjacentstructuresandcausesymptoms.Theyoftengrowbackafterremoval.HistopathologicaldiagnosisAnalysisinlaboratoryofatissuespecimenwiththepurposeoffindingsignsofdisease.

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Histopathological(examination)Thestudyofdiseasedcellsandtissuesusingamicroscopeandothertoolsandmethods.Hypo-fractioned(schedule)radiotherapyRadiationtreatment inwhichthetotaldoseofradiation isdivided into largedosesandtreatmentsaregivenonceadayor lessoften.Hypofractionatedradiotherapy isgivenoverashorterperiodoftime(fewerdaysorweeks)thanstandardradiotherapy*.IDHgene1or2/MutationoftheIDHgene1or2Genes that are mutated in the majority of low grade gliomas* and some secondary high riskgliomas*. In healthy cells they produce enzymes that are important for our bodies’ normalfunctioning, however when the genes are mutated the function of the enzymes they producechanges,ultimatelyproducing substances that create themilieu for cancer initiation.Neverthelesstheroleofthesemutationsincancerneedsfurtherinvestigation.InfiltrativepatternThegrowthpatternthatsomecanceroustissueshave,whentheyinvadenearbyorgans.Infiltrativetumours/infiltratingcancerCancer that has spread beyond the layer of tissue in which it developed and is growing intosurrounding,healthytissues.Alsocalledinvasivecancer.IntermediateprognosisThepotentialoutcomeofthediseaseisnotconsideredgoodorbad,itisplacedinbetween.IntravenouslyIntoorwithinavein.Intravenoususuallyreferstoawayofgivingadrugorothersubstancethroughaneedleortubeinsertedintoavein.AlsocalledIV.IonisingradiationAtypeofradiationmade(orgivenoff)byX-rayprocedures,radioactivesubstances,raysthatenterthe Earth's atmosphere from outer space, and other sources. At high doses, ionizing radiationincreaseschemicalactivityinsidecellsandcanleadtohealthrisks,includingcancer.IrradiationTheuseofhigh-energyradiationfromX-rays,gammarays,neutrons,protons,andothersourcestokillcancercellsandshrinktumours.Radiationmaycomefromamachineoutsidethebody(external-beamradiotherapy*),oritmaycomefromradioactivematerialplacedinthebodynearcancercells(internal radiotherapy*). Systemic irradiation uses a radioactive substance, such as a radiolabelledmonoclonalantibody,thattravelsinthebloodtotissuesthroughoutthebody.Alsocalledradiationtherapyandradiotherapy*.LamotrigineAdrugthatisusedtotreatpartialseizures*inthecaseofepilepsyandalsototreatbipolardisorderasamoodstabilizer.Itisbeingstudiedinthepreventionofperipheralneuropathy*causedbysomechemotherapy*drugs.Itbelongstothefamilyofdrugscalledanticonvulsants.

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LevetiracetamAdrugusedtotreatseizures*(involuntarymusclemovements)causedbyepilepsy(agroupofbraindisorders).Levetiracetamisbeingstudiedinthetreatmentofseizures*inpatientswithcancerthathasspreadtothebrain.Itisatypeofanticonvulsant.Li-FraumenisyndromeA rare, inherited predisposition to multiple cancers, caused by an alteration in the p53 tumoursuppressorgene.LomustineAdrugusedtotreatbraintumoursthathavealreadybeentreatedwithsurgeryorradiotherapy*.ItisalsousedtotreatHodgkinlymphomathathasnotgottenbetterwithothertypesoftreatmentorhascomeback.Itisbeingstudiedinthetreatmentofothertypesofcancer.Lomustinedamagesthecell'sDNAandmaykillcancercells.Itisatypeofalkylatingagent*.Low-molecular-weightheparinA class of anticoagulant medication. Its particular molecular structure makes its effects morepredictablethannaturallyoccurringheparin.LynchsyndromeAninheriteddisorderinwhichaffectedindividualshaveahigher-than-normalchanceofdevelopingcolorectalcancerandcertainothertypesofcancer,e.g.endometrialcancer,gastriccancer,ovariancancer, pancreatic cancer, bladder cancer, kidney cancer, or brain tumour amongst others. AlsocalledhereditarynonpolyposiscoloncancerandHNPCC.MagneticResonanceImaging(MRI)An imaging technique that is used inmedicine. It usesmagnetic resonance. Sometimes, a fluid isinjected that enhances the contrast between different tissues to make structures more clearlyvisible.Malignancies/malignantgliomaMalignant is used to describe a severe and progressively worsening disease. Amalignant tumourgrows fast invading surrounding tissues and spreading to other parts of the body. A malignanttumourisasynonymforcancer.MedulloblastomaAmalignantbraintumourthatbeginsinthelowerpartofthebrainandthatcanspreadtothespineor to other parts of the body. They are the most common type of malignant brain tumours inchildren.Medulloblastomasareatypeofprimitiveneuroectodermaltumour(PNET).MeningesThethreethinlayersoftissuethatcoverandprotectthebrainandspinalcord*.Meningioma(s)A type of slow-growing tumour that forms in the meninges (thin layers of tissue that cover andprotectthebrainandspinalcord*).Meningiomasusuallyoccurinadults.

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MeningitisInflammation of the meninges* (three thin layers of tissue that cover and protect the brain andspinalcord*).Meningitis isusuallycausedbyabacterialorviral infection,butsometimesiscausedbycancer,drugallergies,orinflammatorydiseases.MetastasisThe spread of cancer from one part of the body to another. A tumour formed by cells that havespreadiscalledametastatictumourorametastasis.Themetastatictumourcontainscellsthatarelikethoseintheoriginaltumour.MGMTgenemethylationMethylation isachemical reactionbywhichagenecalledMGMT is inactivated.Whenthisgene isactive ithelpscellstorepairDNAdamage,butwhenit is inactivecellsarenotcapableofrepairingtheirDNA.MolecularcharacteristicsInglioma*,itreferstothepresenceofMGMTgenemethylation*.MolecularmarkersA biological molecule found in blood, other body fluids, or tissues that is a sign of a normal orabnormalprocess,orofaconditionordisease.Amolecularmarkermaybeusedtoseehowwellthebody responds to a treatment for a disease or condition. Also called biomarker and signaturemolecule.NeurofibromatosistypeIAraregeneticconditionthatcausesbrownspotsandtumoursontheskin,frecklinginskinareasnotexposed to the sun, tumours on the nerves, and developmental changes in the nervous system,muscles,bone,andskin.AlsocalledNF1.NeurologicalexaminationAseriesofquestionsandteststocheckbrain,spinalcord*,andnervefunction.Theexamchecksaperson’smentalstatus,coordination,abilitytowalk,andhowwellthemuscles,sensorysystems,anddeeptendonreflexeswork.Neurologicalstatus/conditionTheextenttowhichthenervoussystemreactstoexternalstimuli.Asystematicexaminationduringthephysicalexaminationallowsdoctorstohaveinformationonthefunctioningofthenerves.NeuropathologistApathologistwhospecializesindiseasesofthenervoussystem.Apathologist*identifiesdiseasebystudyingcellsandtissuesunderamicroscope.NitrosoureaAn anticancer drug that can cross the blood-brain barrier. Carmustine and lomustine* arenitrosoureas.

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OccipitallobeThesmallestoffourpairedlobesinthehumancerebralcortex.Itislocatedintherearmostportionoftheskullanditsfunctionsarerelatedtosight,asitcontainsthevisualprocessingcenter.OedemaAnabnormalcollectionoffluidbeneaththeskinorinabodycavitywhichcausesswelling.Oedemainthe brain causes symptoms such as nausea, vomiting, blurred vision, faintness; and sometimesseizures*andcoma.OligoastrocytomaA brain tumour that forms from both oligodendrocytes* and astrocytes*,which are types of glialcells(cellsthatcoverandprotectnervecells inthebrainandspinalcord*andhelpthemworkthewaytheyshould).Anoligoastrocytomaisatypeofmixedglioma*.Oligodendrocytes/OligodendrogliomaArare,slow-growingtumourthatbeginsinoligodendrocytes(cellsthatcoverandprotectnervecellsinthebrainandspinalcord*).Alsocalledoligodendroglialtumour.OpenbiopsyAprocedureinwhichasurgicalincision(cut)ismadethroughtheskintoexposeandremovetissues.Thebiopsytissueisexaminedunderamicroscopebyapathologist*.Anopenbiopsymaybedoneinthedoctor’sofficeor in thehospital,andmayuse localanaesthesiaorgeneralanaesthesia. In thecaseofbraintumour,itisanactualsurgery,sogeneralanaesthesiaisrequired.PathogensAmicroorganism,suchasvirusorbacteria,thatcausesdisease.PathologistA doctor specialized in histopathology which is the study of diseased cells and tissues using amicroscope.PCVregimenAnabbreviationforachemotherapy*combinationusedtotreatcertaintypesofbraintumours.Itisoften used with radiotherapy*. It includes the drugs procarbazine hydrochloride*, lomustine*(CCNU),andvincristinesulfate*.PerformancestatusTheperformancestatusevaluatesthepatient’sphysicalabilitiesbygivingascorefrom0,forafullyactivepatient,to4forapatientwhoiscompletelydisabledduetohis/herdisease.PeripheralneuropathyA nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in differentparts of the body. It usually begins in the hands or feet and gets worse over time. Peripheralneuropathymaybe causedby physical injury, infection, toxic substances, disease (such as cancer,diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also calledneuropathy.

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PituitaryglandThemainendocrine gland in thebrain. It produceshormones that control other glands andmanyotherfunctionsincludinggrowth.(Seepictureinpage23)PlateletsSmallcellfragmentsthatplayafundamentalroleintheformationofbloodclots.Patientswithalowplateletcountareatriskofseverebleeding.Patientswithahighcountareatriskofthrombosis,theformationofbloodclotsthatcanblockbloodvesselsandresultinstrokeorothersevereconditions,andcanalsobeatriskofseverebleedingbecauseofplateletdysfunction.PregabalinAdrugusedtotreatnervepaincausedbydiabetesorherpeszoster infectionandcertain typesofseizures*.Itisbeingstudiedinthepreventionandtreatmentofnervepaininthehandsandfeetofcancerpatientsgivenchemotherapy*.Pregabalinisatypeofanticonvulsant.ProcarbazineTheactiveingredientinadrugthat isusedtotreatadvancedHodgkinlymphomaandisbeingusedandstudiedinthetreatmentofothertypesofcancer.ProcarbazineblockscellsfrommakingproteinsanddamagesDNA.Itmaykillcancercells.Itisatypeofantineoplasticagentandatypeofalkylatingagent*.PrognosisThelikelyoutcomeorcourseofadisease;thechanceofrecoveryorrecurrence*.PseudoprogressionAs a reaction to chemoradiotherapy* a brain tumour might look bigger than previous to thetreatment in imaging tests. This could happen if the imaging is taken just some weeks after thetreatment is finished. It might not be progression but a reaction of tumoural tissues to damagecausedbythetreatment.Thatiswhyitisnecessarytorepeatinitialimagingsomemoreweekslatertoconfirmwhetheratumourisactuallyprogressingorthattheapparentprogressionwasjusttissuereactiontodamagebutthetumourmightactuallyberegressing.Radicalresection/surgerySurgery that is extensive and aims to remove as much tumour tissue as possible, as well assurroundingtissue.RadiologicaldiagnosisVisualizationofatumourorlesioninimagingtests.RadiologicalexaminationTest that uses imaging technology (such as radiography, ultrasound, computed tomography andnuclearmedicine) tovisualizeorgans, structuresand tissueswithin thebody tobothdiagnoseandtreatdiseases.

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RadiotherapyAtherapy inwhich radiation (high-energyX-rays) isused in the treatmentof cancer that isalwaysoriented to the specific location of the cancer. Radiotherapy can be administered internally orexternally.Whenitisinternal,asourceofradiation(radioactivematerial)isinsertedinsidethebodycavityornearthetumour,theradioactiveenergyofthatsourceatsomepointwilldecrease;whenradiotherapyisadministeredexternallyamachinegeneratestheradioactiveenergythatistargetedtothetumourintheformofbeams.RecurrenceCancer or disease that has come back, usually after a period of time during which the cancer ordiseasewasnotpresentorcouldnotbedetected.Alsocalledrecurrentcancerordisease.RedbloodcellThemostcommontypeofbloodcell.Itisthesubstancethatmakesthebloodappearred.Theirmainfunctionisthetransportofoxygen.ResidualdiseaseCancercellsthatremainafterattemptstoremovethecancerhavebeenmade.SeizuresSudden,uncontrolledbodymovements and changes inbehaviour thatoccurbecauseof abnormalelectrical activity in the brain. Symptoms include loss of awareness, changes in emotion, loss ofmuscle control, and shaking. Seizuresmay be caused by drugs, high fevers, head injuries, certaindiseases,suchasepilepsyandbraintumours.SpinalcordA column of nerve tissue that runs from the base of the skull down the centre of the back. It iscoveredbythreethinlayersofprotectivetissuecalledmembranes.Thespinalcordandmembranesare surroundedby the vertebrae (backbones). The spinal cordand thebrainmakeup the centralnervoussystem(CNS).Spinalcordnervescarrymessagesbetweenthebrainandtherestofthebody.Stereotacticbiopsy/proceduresAbiopsyprocedurethatusesacomputeranda3-dimensionalscanningdevicetofindatumoursiteandguidetheremovaloftissueforexaminationunderamicroscope.Symptomaticmedication(s)Drugsthatareusedtotreatsymptomsandsignsofadiseasewithoutfightingthecauseinitself.Targetedagents/therapyA type of treatment that uses drugs or other substances to identify and attack specific types ofcancer cells with less harm to normal cells. Some targeted therapies block the action of certainenzymes,proteins,orothermoleculesinvolvedinthegrowthandspreadofcancercells.Othertypesoftargetedtherapieshelptheimmunesystemkillcancercellsordelivertoxicsubstancesdirectlytocancercellsandkillthem.Targetedtherapymayhavefewersideeffectsthanothertypesofcancertreatment.Mosttargetedtherapiesareeithersmallmoleculedrugsormonoclonalantibodies.

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TemozolomideTemozolomide belongs to a group of anticancermedicines called alkylating agents*. In the body,temozolomideisconvertedtoanothercompoundcalledMTIC.MTICbindstotheDNAofcellswhiletheyare reproducing,which stops cell division.Asa result, the cancer cells cannotdivide, slowingdownthegrowthoftumours.TemporallobeEach of two lobes of the brain, localised at the bottom middle part of cortex, right behind thetemples.The temporal lobe is involved in processing sensory input into derivedmeanings for theappropriateretentionofvisualmemories,languagecomprehension,andemotionassociation.Thromboembolic(events)Formationofbloodclot(s)inbloodvessels,whichdetachandarecarriedawaybythebloodstreamto plug another vessel. It could be a vessel in the lungs, brain, gastrointestinal tract, kidneys, orextremities.TopiramateDrugthatisusedtotreatseizuresandmigraines.TurcotsyndromeCondition in which cells in the colon become abnormal and formmasses called polyps. It is alsocharacterisedbynervoussystemtumours.VincristineTheactive ingredient inadrugusedtotreatacute leukaemia. It isused incombinationwithotherdrugs to treat Hodgkin disease, non-Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma, andWilmstumour.Vincristineisalsousedandstudiedinthetreatmentofothertypesofcancer.Itblockscellgrowthbystoppingcelldivision.Itisatypeofvincaalkaloidandatypeofantimitoticagent.WarfarinAdrugthatpreventsbloodfromclotting.Itbelongstothefamilyofdrugscalledanticoagulants.WhitebloodcellsCellsoftheimmunesystemthatareinvolvedinthebody'sdefenceagainstinfections.

The ESMO / Anticancer Fund Guides for Patients are designed to assist patients, their relatives and caregivers to understand the nature of different types of cancer and evaluate the best available treatment choices. The medical information described in the Guides for Patients is based on the ESMO Clinical Practice Guidelines, which are designed to guide medical oncologists in the diagnosis, follow-up and treatment in different cancer types.These guides are produced by the Anticancer Fund in close collaboration with the ESMO Guidelines Working Group and the ESMO Cancer Patient Working Group.

For more information please visit www.esmo.org and www.anticancerfund.org

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