Very Long-Term Sequelae of Craniopharyngioma
European Journal of Endocrinology 10.1530/EJE-17-0044 approaches andweregenerallymorefrequentinpatients withchildhood-comparedadult-onsetdisease. Conclusions similar betweenpatientswithchildhood-andadult-onset craniopharyngioma. initial craniopharyngiomatreatmentwithcystaspiration comparedwithothertherapeuticapproaches.Survivalwas compared withpatientsadult-onsetdisease.Recurrence-/progression-freesurvivalwassignificantlylower after hormone deficiency, diabetesinsipidus, panhypopituitarism,morbidobesity, epilepsyandpsychiatricconditions long-term healtheffects. Patientswithchildhood-onsetcraniopharyngiomaexperiencedsignificantlymoregrowth long-term healthconditionsobserved.Different initialcraniopharyngiomatreatmentapproachesresultedinsimilar Results without radiotherapy( ( (interquartile range:5–23 years).Initialcraniopharyngiomatreatmentapproachesincludedgrosstotalresection (63 patientswithchildhood-onsetdisease).Medianfollow-upsincecraniopharyngiomapresentationwas13 years Methods Design age groupatcraniopharyngiomapresentation. spectrum oflong-termhealtheffects inpatientswithcraniopharyngiomaaccordingtoinitialtreatmentapproachand and adult-onsetcraniopharyngiomareportconflictingresults.Theobjectiveofthisstudywastoanalyseafull treatment approach.Inaddition,studiescomparinglong-termhealthconditionsbetweenpatientswithchildhood- follow-up durationsandgenerallydonotcomparelong-termhealtheffects accordingtoinitialcraniopharyngioma Objective Abstract Pituitary CentreRotterdam,ErasmusUniversityMedical Centre,theNetherlands Carolien M van Rij van Veelen-Vincent Coriene E Catsman-Berrevoets Mark Wijnen Very long-termsequelaeofcraniopharyngioma Hospital, Rotterdam,theNetherlands, 4 Hospital, Rotterdam, the Netherlands, Rotterdam, the Netherlands, 1 Department of PaediatricNeurology, Section Endocrinology, DepartmentofMedicine,PituitaryCentreRotterdam,ErasmusUniversityMedicalCentre, n DOI: 10.1530/EJE-17-0044 www.eje-www.eje-online.org Clinical Study
= 25), subtotalresectionwithoutradiotherapy( : Cross-sectionalstudybasedonretrospectivedata. : Pituitaryhormonedeficiencies(98%),visualdisturbances(75%)andobesity(56%)werethemostcommon online.org : We studiedasingle-centrecohortof128patientswithcraniopharyngioma treatedfrom1980onwards : Studiesinvestigatinglong-termhealthconditionsinpatientswithcraniopharyngiomaarelimitedbyshort : Long-termhealthconditionswerecomparableafterdifferent initialcraniopharyngiomatreatment 1 ,
2 , Marry Mvan den Heuvel-Eibrink 7 , Aart-Jan van der Lely 5 , Alof H G Dallenga 2 n Department ofPaediatricOncology/Haematology, ErasmusMC–SophiaChildren’s ) and =8), © 2017EuropeanSociety ofEndocrinology © 2017EuropeanSociety ofEndocrinology 5 6 3 Department ofPaediatricNeurosurgery, ErasmusMC–SophiaChildren’s Department ofNeurosurgery, and Princess MaximaCentreforPaediatricOncology, Utrecht,theNetherlands, 4 M Wijnenandothers , Erna M C Michiels , Erna M C 90 Yttrium brachytherapy( Printed inGreatBritain 6 , J Herbert van den Berge 1 and n Sebastian J C M M Neggers
= 2 , 44), subtotalresectionwithradiotherapy( 3 2 , Joseph A M J LJanssen , Marie-Lise C 7 Department ofRadiationOncology, n =21). Sequelae ofcraniopharyngioma Published byBioscientifica Ltd.
6 , 1 1 , 2 , Downloaded fromBioscientifica.com at09/28/202102:26:01PM (2017) Endocrinology European Journal of [email protected] Email to MWijnen should beaddressed Correspondence n 176 5, yt aspiration cyst =25), 176 : 6 176 :6 , 755–767
755 –767 via freeaccess European Journal of Endocrinology presentation. treatment approachandage groupatcraniopharyngioma accordingtoinitial patients withcraniopharyngioma a full spectrumof long-term health conditions in conflicting results( report childhood- andadult-onsetcraniopharyngioma comparing long-termhealtheffectsbetweenpatientswith treatment approach ( health conditionsaccording to initial craniopharyngioma Furthermore, only a few studies compare long-term ten years( are limitedbyshortfollow-updurationsoflessthan term healtheffectsinpatientswithcraniopharyngioma impair qualityoflife( ( conditions relatedtotumourandtreatmentarefrequent 95% ( ratesbetween40and encouraging 10-yearoverallsurvival cyst decompression( approachcomprisinglimitedresectionorconservative 12 hypothalamic andopticfunctions( favour initialextensiveexcisionwherebypreserving approach variesfromcentreto( characteristics, the aggressiveness ofthetherapeutic individualized basedontumourandpatient treatmentispredominantlycraniopharyngioma ( as wellstereotacticradiosurgery emitting isotopes or chemotherapeutic substances, treatment optionsincludeintracysticapplianceofbeta- or without postoperative radiotherapy. Alternative generally treatedwithneurosurgicalexcision and visualpathways( systemstructures, likethehypothalamic–pituitary due tocloseproximityofthetumourvitalbrain and treatment-related morbidity. This is challenging qualityoflifebyminimizingtumour-while preserving anddiseasecontrolaims toprovidelong-termsurvival approach ( their aetiology, pathogenesisandoptimaltherapeutic by Von Zenker( yearsofage( 40–44 adults, andhavepeakincidencesbetween5–9 and fluid-filledcysts( of epithelialhistologythatoftenexhibitcalcifications arebenign(supra)sellartumoursCraniopharyngiomas Introduction www.eje-online.org 10 Clinical Study , , The objectiveofthepresentstudyistoanalyse Although recent studies on craniopharyngioma report Although recentstudiesoncraniopharyngioma 20 13 10 , , 22 , 14 , 21 4 10 23 , ). In general, craniopharyngioma treatment). Ingeneral,craniopharyngioma , 15 , , 22 24 20 ), whileothercentrespreferamore 3 , , , ), therehasbeenacontroversyabout 26 23 28 22 , , , 16 28 2 17 27 , 1 30 24 ). Since their discovery in1857). Sincetheirdiscovery ). Theyaffectbothchildrenand 23 , , , , , , 32 17 28 1 35 , 36 25 ). Craniopharyngiomas are). Craniopharyngiomas ). Moststudiesassessinglong- , , 24 , ). 29 18 ), seriouslong-termhealth 36 , , , 25 , 30 M Wijnenandothers 19 37 , , , 31 26 ). Moreover, studies 20 ), andsignificantly , ). 7 6 27 , ). Somecentres 5 8 , ). Although , 32 9 , , 33 10 , , 34 11 ). , subdivided ingrosstotal resection( treatmentapproacheswere Initial craniopharyngioma Craniopharyngioma treatment 1990 respectively. imaging becameavailableinourinstitution1976and solid. Computed tomography and magnetic resonance consistency was characterized as unicystic, multicystic or or bothintra-andsuprasellar. Craniopharyngioma localization wasdefinedasintrasellar, suprasellar reports.Craniopharyngioma and neurosurgery consistency atdiagnosiswereobtainedfromneuroimaging localization and Data regardingcraniopharyngioma Craniopharyngioma localizationandcharacteristics wereextractedfromthemedicalrecords. survival consistency, treatment,long-termhealthconditionsand symptoms, hydrocephalus,tumourlocalizationand verified. Dataregardingbaselinecharacteristics,presenting werehistologically of allbutthreecraniopharyngiomas years).Diagnoses years(interquartilerange:5–23 of 13 between 1978and2015werefollowed-upforamedian adult-onset). Patientspresentingwithcraniopharyngioma age (i.e.childhood-onset),and65were Data collection informed consent. board approvedthisstudyandallpatientsgavetheir from 1980onwards.Ourlocalinstitutionalreview treatedto include only patients with craniopharyngioma treatment, neuroimagingandsupportivecare,wechose to time-relateddifferencesincraniopharyngioma reduce heterogeneity in our study population attributable sectional studybasedonretrospectivedata.Inorderto Centre wereeligibleforparticipationinthiscross- attheErasmusUniversityMedical craniopharyngioma Patients whowerediagnosedwithand/ortreatedfor Participants Subjects andmethods 1980 onwards.Ofthese128patients,63were of whom 128 were treated from with craniopharyngioma electronic patientfiles.Thissearch yielded145patients Patients wereidentifiedbyacomputer-basedsearch inthe Sequelae ofcraniopharyngioma Downloaded fromBioscientifica.com at09/28/202102:26:01PM 176 ≥ 18 years ofage(i.e. :6 n 5, subtotal =25), < 18 years of 756 via freeaccess European Journal of Endocrinology the craniopharyngioma. completely removedduring neurosurgicalexcisionof glandwasin allpatients.Intenpatients, thepituitary functiontestingwere confirmedbyformal pituitary hormonedeficienciesdisordered breathing.Pituitary by polysomnographyinpatientswithsuspectedsleep mass index.Obstructivesleepapnoeawasdiagnosed files. Weight statuswasclassifiedaccording tobody considered tobepresentifdocumentedinthepatient Cognitive impairmentandbehaviouralchangeswere independent dailylivingwereclassifiedassevere. were classified asmild and deficits thatcompromised independent dailyliving.Deficitsthathadnoimpact (i.e. mildandsevere)basedontheirreportedimpact Neurological deficits were classified into two categories defects werediagnosedwithGoldmannperimetry. correction forrefractiondisorders. Visual field examinations. Visual acuitywasdeterminedafter disturbances werediagnosedbasedonophthalmic reflecting long-termhealthconditions. Visual cerebrovascular eventswerestudiedasoutcomes neoplasmsandcardio- deficiencies, secondary hormonestatus, obstructivesleepapnoea,pituitary treatment (postoperativedeliriumexcluded),weight behavioural changes,psychiatricconditionsrequiring neurological deficits,cognitiveimpairment, Visual disturbances,epilepsyrequiringtreatment, Long-term healthconditions and neuroradiology. neurology, paediatriconcology, radiation-oncology neurosurgery, (paediatric)endocrinology, paediatric meetingsbyspecialistsin(paediatric) multidisciplinary nineties, allpatientsweresystematicallydiscussedin based onthetreatingphysicians’preferences.Since In eachpatient,theinitialtherapeuticapproachwas without residualdiseaseonpostoperativeimaging. asdocumentedbytheneurosurgeon, craniopharyngioma resection wasdefinedasthecompleteremovalof treatmentapproach.Grosstotal craniopharyngioma were excludedfromtheanalysesaccordingtoinitial with radiotherapy( approaches (radiotherapyonly( and twopatientsweretreatedwithothertherapeutic excision buthadanunknowndegreeofresection ( without radiotherapy( resection withradiotherapy( resection withoutradiotherapy( n Clinical Study
= 21). Threepatientsweretreatedwithneurosurgical n n
= 8) and =8) 1)). Theselatterfivepatients 90 M Wijnenandothers n 5, yt aspiration cyst =25), Yttrium brachytherapy n ) cs aspiration cyst =1), n 4, subtotal =44), were described as median and interquartile range; discrete were describedasmedianandinterquartilerange;discrete Package forSocialSciences(SPSS24).Continuousvariables Statistical analyseswereperformedusingthe Statistical analysis itselfornot. craniopharyngioma cause ofdeathwasclassifiedasdirectlyrelatedtothe on physician’s preferenceandclinicaljudgement.The Follow-up neuroimaging was performed regularly, based irradiation, cystaspirationor aftersubtotalresection, of thecraniopharyngioma total resection.Progressionwasdefinedasre-growth aftergross as reappearanceofthecraniopharyngioma diagnosed withneuroimaging.Recurrencewasdefined recurrence/progression was Craniopharyngioma treatment. calculated since initial craniopharyngioma were Overall and recurrence-/progression-free survival Survival influence of treatment decade on survival by log-rank bylog-rank influence oftreatmentdecade onsurvival duration asindependentvariables. We investigatedthe regression models including treatment decade and follow-up of long-termhealtheffects usingmultivariablelogistic treatmentonthedevelopment initial craniopharyngioma 1999, 2000–2009,or≥2010)andfollow-updurationsince influence ofthetreatmentdecade(i.e.1980–1989,1990– neuroimaging and supportive care, we investigated the may haveevolvedovertimeduetoadvancesintreatment, management period, and because craniopharyngioma may onlybecomeapparentafteraprolongedfollow-up differences. Becausecertainlong-termhealthconditions post hoc concerning morethantwogroups,Bonferroni-corrected Incasestatisticalsignificancewasreachedinavariable curves. methods. Log-ranktestswereusedtocomparesurvival wereestimatedbyKaplan–Meier progression-free survival the assumptionswerenotmet.Overallandrecurrence-/ ratio statisticsorFisher’s exacttestswereusedincase discrete variables.Mann–Whitney t weremade by Student’sadult-onset craniopharyngioma used. Comparisonsbetweenpatientswithchildhood-and met, Kruskal–Wallis testsandlikelihoodratiostatisticswere for discrete variables. In case the assumptions were not of varianceforcontinuousvariablesandChi-squaredtests treatment approachwereperformedbyone-wayanalyses Comparisons accordingtoinitialcraniopharyngioma were based on the number of patients with available data. variables asfrequenciesandpercentages. Evaluations Sequelae ofcraniopharyngioma -test for continuous variables and Chi-squared tests for -test forcontinuousvariablesandChi-squaredtests analyses were performed to specify subgroup-related analyseswereperformedtospecifysubgroup-related Downloaded fromBioscientifica.com at09/28/202102:26:01PM 90 Yttrium brachytherapy. U tests and likelihood testsandlikelihood 176 www.eje-online.org :6 757 via freeaccess European Journal of Endocrinology www.eje-online.org insipidus was found in 7% of the patients. Underweight insipidus wasfoundin7%ofthepatients.Underweight deficiency anditaffected60%ofthepatients.Diabetes hormone hypogonadism wasthemostcommonpituitary and 68%ofthepatientsrespectively. Hypogonadotropic common disease manifestations and occurred in 87, 71, hormone deficienciesandheadacheswerethemost neurosurgical excision,the neurosurgicalapproach In thepatientswhowere initiallytreatedwith Craniopharyngioma treatment approaches ( treatmentbetween different initial craniopharyngioma tumour characteristicswerenotsignificantlydifferent vs 18%, (40%compared with adult-onset craniopharyngioma significantly morecommoninpatientswithchildhood- and/or thirdventricleinvolvementwerealso 21%; childhood- comparedwithadult-onsetdisease(45%vs in patients with multicystic craniopharyngiomas analyses revealedasignificantlyhighernumberof Bonferroni-corrected craniopharyngioma. between patientswithchildhood-andadult-onset Table 1 Tumour characteristicsatdiagnosisaredepictedin Craniopharyngioma characteristicsatdiagnosis childhood-onset craniopharyngioma. more commoninpatientswithadult-compared hypothyroidism (56%vs32%, (39%vs16%, overweight P Visualcraniopharyngioma. fielddefects(85%vs59%, 27%, significantly moregrowthhormonedeficiency(53%vs presented with childhood-onsetcraniopharyngioma presentedwithblindness.Patients craniopharyngioma) respectively. Two patients(bothwithchildhood-onset and obesityaffected10%12%ofthepatients are shownin Presenting symptomsinpatientswithcraniopharyngioma Presenting symptoms Results statistically significant. tests for trend. A
< Clinical Study
0.01), cognitive impairment (16% vs 3%, P P
. Tumour consistencywassignificantlydifferent < =
0.02). Hydrocephalus,aswellhypothalamic 0.01) comparedwithpatientsadult-onset P
<
Table 2 0.01; 66% vs 42%, Table 1 P -value ). . Visual disturbances,pituitary < 0.05 (two-tailed) was considered 0.05 (two-tailed) was considered P P
<
< M Wijnenandothers
0.01) weresignificantly
0.01) and secondary 0.01) andsecondary P .1. ain and Patient =0.01). post hoc P =0.02),
dose was 54 with radiotherapy, themediancumulativeradiation was missing.Inthepatientswhowereinitiallytreated patients, detailedinformationonthetypeofradiotherapy and stereotacticradiotherapyto16patients.Infour external beamradiotherapywasappliedtoeightpatients patients whoinitiallyreceivedradiotherapy, conventional Inthe childhood- andadult-onsetcraniopharyngioma. were notsignificantlydifferentbetweenpatientswith treatment approaches,aswellneurosurgicalapproaches resection withradiotherapy. Initialcraniopharyngioma subtotal resectionwithoutradiotherapyand used between patientstreated with gross total resection, significant differencesintheneurosurgicalapproaches the neurosurgicalapproachweremissing.Thereno one patient(1%).Infivepatients(5%)dataregarding transcallosal intwopatients(2%)andsupra-orbital in 31patients(35%),pterional20(23%), was transsphenoidalin35patients(39%),subfrontal external beam radiotherapy at an age of 41 years. Three external beamradiotherapy atanageof41 years. radiation encephalopathy six years after conventional itself. One patient developed the craniopharyngioma severe neurologicaldeficits weredirectlyrelatedto daily living)affected11 patients. Inthreepatients, neurological deficits(i.e.compromisingindependent initial treatmentwith after initial treatment with subtotal resection; one after the patients.Fivepatientsdemonstratedblindness(four the patients. Diabetes insipidus was diagnosed in 61% of hormonedeficiencyandwas foundin92%of pituitary Hypogonadotropic hypogonadismwasthemostcommon affected 98,75and56%ofthepatientsrespectively. were themostcommonlong-termhealtheffectsand hormone deficiencies,visualdisturbancesandobesity are shown in craniopharyngioma Long-term health conditions in patients with Long-term healthconditions was predominantlyusedduring1980–1989. 1980–1989 to71%in (with orwithoutradiotherapy)increasedfrom30%during 12% in total resectiondeclinedfrom22%during1980–1989to treatment changedovertime( 1–6 months). and radiotherapywastwomonths(interquartile range: fractions). Themediandurationbetweenneurosurgery in amedian30fractions(interquartilerange:30–30 Sequelae ofcraniopharyngioma In our institution, initial craniopharyngioma In ourinstitution,initialcraniopharyngioma ≥ 2010. Meanwhile,theuseofsubtotalresection Gy (interquartile range: 54–54 90 ≥ Downloaded fromBioscientifica.com at09/28/202102:26:01PM Yttrium brachytherapy).Severe 2010. i. 1 Fig. 90 Yttrium brachytherapy 176 ). Theuseofgross Table 3 :6 Gy); delivered . Pituitary . Pituitary 758 via freeaccess European Journal of Endocrinology In fourpatients,cerebrovascular events causedsevere 90 after of theinstalledradio-isotope amedian15 months patients suffered from radionecrosis related to leakage Age (year)atpresentation,median(IQR) Female Male n Baseline characteristics Table 1 Weight status (BMI(kg/m Decrease Increase History ofweightchange Epilepsy Headaches *Childhood- vsadult-onset BMI, bodymassindex;IQR,interquartilerange. respectively. consistency, hydrocephalus,hypothalamicand/orthirdventricleinvolvement, andbrainstemcompressionweremissingin5,11,3,1514patients too youngtoreliablyassessgonadalfunction(girls (TSH) in5patients,antidiuretichormone(ADH)4andanterior andcompletepanhypopituitarism(PH)in8patients).Also,42patientswere follicle stimulatinghormone/luteinizinghormone(FSH/LH)in4patients, adrenocorticotropichormone(ACTH)in4patients,thyroidstimulating could notbedeterminedin28patients.Dataregardingpituitaryhormone deficienciesweremissingin8patients(growthhormone(GH)7patients, were missingin6patients.Dataregardingvisualacuitydisordersand fielddefectsweremissingin28and31patientsrespectively. Weight status Data regardingheadaches,epilepsy, neurologicaldeficits,alteredlevelof consciousness, cognitiveimpairment,behaviouralchangesandweightchange Brain stemcompression Hypothalamic and/orthirdventricleinvolvement Presence ofhydrocephalus Solid Multicystic Unicystic Consistency Intra-/suprasellar Suprasellar Intrasellar Localization ADH TSH ACTH FSH/LH GH Pituitary hormonedeficiencies Presenting symptoms Tumour characteristics tru rcyhrp tamda g f5 years. Yttrium brachytherapyat a medianageof54 Clinical Study Overweight (25.0–29.9) Normal weight(18.5–24.9) Underweight ( Behavioural changes Cognitive impairment Altered levelofconsciousness Neurological deficits Visual fielddefects Visual acuitydisorders Complete PH Anterior PH Class I–IIIobesity( Class IIIobesity( Class IIobesity(35.0–39.9) Class Iobesity(30.0–34.9) Baseline characteristics,presentingsymptoms,andtumourcharacteristicsatdiagnosis.Dataarepresentedas < 18.5) ≥ 40.0) ≥ 30.0) 2 )) M Wijnenandothers < 14 years ofage;boys All craniopharyngiomas < 15 years ofage).Dataregardinginitialcraniopharyngiomalocalization, who experiencedacerebral infarction oftheentire left years.Thislattergroupincluded onechild age of27 treatmentatamedian after initialcraniopharyngioma neurological dysfunction a mediansevenmonths Sequelae ofcraniopharyngioma 19 (8–42) 71 (56) 13 (11) 15 (12) 12 (10) 26 (21) 42 (34) 72 (74) 73 (73) 83 (68) 57 (45) 27 (27) 51 (51) 10 (10) 19 (16) 17 (14) 54 (44) 42 (34) 49 (60) 48 (40) 87 (71) 12 (12) 16 (14) 60 (53) 36 (29) 38 (33) 71 (61) 70 (57) 48 (39) 7 (6) 7 (7) 5 (4) 4 (3) 8 (7) 3 (3) 2 (2) 8 (7)
128 Childhood-onset 38 (60) 31 (61) 15 (25) 25 (42) 23 (59) 33 (72) 42 (71) 25 (40) 10 (17) 19 (32) 17 (28) 10 (56) 31 (53) 40 (68) 35 (66) 25 (40) 25 (45) 29 (52) 34 (57) 23 (38) 8 (5–12) 3 (5) 8 (14) 2 (3) 6 (10) 2 (4) 8 (16) 8 (16) 9 (15) 3 (5) 2 (3) 4 (7) 4 (8) 2 (4) 0 (0) 6 (11) 2 (4)
63 Downloaded fromBioscientifica.com at09/28/202102:26:01PM Adult-onset 11 (18) 17 (27) 49 (85) 40 (74) 41 (65) 41 (29–55) 33 (51) 32 (49) 19 (39) 20 (41) 10 (16) 10 (16) 10 (16) 25 (42) 11 (18) 13 (21) 42 (69) 36 (57) 25 (40) 35 (56) 25 (39) 39 (61) 17 (27) 47 (73) 10 (17) 7 (11) 1 (2) 2 (4) 5 (10) 6 (10) 2 (3) 2 (3) 7 (12) 4 (6) 8 (16) 1 (2) 2 (4)
176 65 www.eje-online.org :6
n < < < < < < P (%). -value* 0.28 0.05 0.09 0.14 0.68 0.02 0.28 0.07 0.06 0.01 0.79 0.47 0.01 0.87 1.00 0.39 1.00 0.01 0.21 0.68 0.01 0.49 0.19 1.00 0.24 0.26 0.01 0.39 0.01 0.01 0.02
759 via freeaccess European Journal of Endocrinology www.eje-online.org w/o, without. total resection;RTx, radiotherapy; STR,subtotalresection; percentage; Initial craniopharyngiomatreatment perdecade.%, Figure 1 deficiency (93% vs68%, demonstrated significantlymoregrowthhormone 3 areshownin with adult-onsetcraniopharyngioma health conditionsinpatientswithchildhood-compared a similar patternof long-term health effects. Long-term cyst aspirationand resection, subtotalresectionwithorwithoutradiotherapy, treatmentwithgrosstotal Initial craniopharyngioma treatmentareshownin craniopharyngioma resection. years aftercraniopharyngioma hemisphere withoutaknowncauseapproximatelytwo Female Male n Baseline characteristics are presentedas Table 2 Intrasellar Localization Tumour characteristics Age (year)atpresentation,median(IQR) Multicystic Unicystic Consistency Intra-/suprasellar Suprasellar Solid Presence ofhydrocephalus Hypothalamic and/orthirdventricleinvolvement Brain stemcompression IQR, interquartilerange; compression weremissingin4,9,3,13and12patientsrespectively. Data regardinginitialcraniopharyngiomalocalization,consistency, hydrocephalus,hypothalamicand/orthirdventricleinvolvement,andbrainstem
% . Patientswithchildhood-onsetcraniopharyngioma Clinical Study 100 25 50 75 Craniopharyngioma therapypertreatmentdecade Long-term healthconditionsaccordingtoinitial 0 1980-1989 Patient characteristicsandtumouratdiagnosisaccordingtoinitialcraniopharyngiomatreatment.Data 90 Yttrium, 1990-1999 n (%). 90 90 Yttrium, 90 Yttrium brachytherapyresultedin Yttrium brachytherapy;GTR,gross 2000-2009 P
<
90 0.01), diabetes insipidus (79% Yttrium brachytherapy;GTR,grosstotalresection;RTx, radiotherapy;STR,subtotalresection;w/o,without.
M Wijnenandothers 201 0 90 Cyst aspiration STR with STR w/o GT Yttriu R Table 4 m 15 (8–37) 16 (64) 15 (65) 13 (57) 11 (48) RT Table RT 1 (4) 9 (36) 9 (39) 7 (30) 1 (4) 6 (25) 2 (9)
GTR
25 x x . resection, subtotalresection with orwithoutradiotherapy, treatment with grosstotal after initialcraniopharyngioma wascomparable of follow-up.Althoughoverall survival years was90,74and52%at5,1020 free survival yearsoffollow-up.Recurrence-/progression- 10 and20 Figs 2 treatment areshownin initial craniopharyngioma after Overall and recurrence-/progression-free survival Survival decade (OR:0.9,95%CI:0.81–0.98; neurological deficitsafteradjustmentfortreatment associated with a significantly lowerrisk ofsevere presentationwas duration aftercraniopharyngioma follow-up duration. In addition, a prolonged follow-up (OR: 0.4,95%CI:0.21–0.97; (CI): 0.12–0.86; obesity (oddsratio(OR):0.3,95%confidenceinterval decades resultedinsignificantreductionsofmorbid (26% vs5%, compared withchildhood-onsetcraniopharyngioma were significantly more commonin patients with adult- Cardio-andcerebrovascularevents craniopharyngioma. 23%, (32% vs15%, P 61%, vs 43%, STR w/oRTx Sequelae ofcraniopharyngioma
< 26 (9–41) 25 (57) 19 (43) 14 (35) 23 (58) 28 (65) 14 (33) 10 (23) 20 (50)
1 (2) 3 (8) 4 (10) 0.01), morbid obesity (24% vs 6%,
Initial craniopharyngioma treatmentinmorerecent Initial craniopharyngioma 44 P and P
=
< 0.03), complete panhypopituitarism (66% vs 34%,
P 0.01) comparedwithpatientsadult-onset
< 3 STR withRTx
0.01), anteriorpanhypopituitarism(79%vs . Overall survival was93,85and77% at 5, . Overallsurvival P 14 (56) 11 (44) 26 (15–46) 15 (65) 14 (58) 15 (68) P
< 1 (4) 9 (38) 6 (26) 2 (9) 5 (21) 4 (17)
= 0.01). 25 P 0.03) andpsychiatricconditions(56%vs
= 0.02) andsevereneurologicaldeficits Downloaded fromBioscientifica.com at09/28/202102:26:01PM Cyst aspiration 13 (5–71) 5 (63) 3 (38) 0 (0) 3 (38) 5 (63) 3 (38) 5 (63) 0 (0) 6 (75) 5 (63) 1 (13) P
= 8 0.04) afteradjustmentfor P 176 =0.02). P :6 90
< 11 (6–45) 12 (57) 13 (65) 10 (48) 10 (48) Yttrium 9 (43) 1 (5) 7 (35) 0 (0) 7 (33) 7 (41) 4 (24) .1, epilepsy 0.01),
21 P 760 -value 0.84 0.38 0.69 0.81 0.28 0.18 0.65
via freeaccess European Journal of Endocrinology Weight status (BMI(kg/m Psychiatric conditions Behavioural changes Cognitive impairment Severe Mild Neurological deficits: Epilepsy Visual fielddefects Visual acuitydisorders Age (years)atfollow-up,median(IQR) Follow-up (years)sincepresentation,median(IQR) n BMI, bodymassindex;IQR,interquartilerange. **Childhood vsadult-onset ( cancer ( fibroadenoma ( * in 6patients,andcompletePH1patient).Also,8patientsweretooyoungtoreliablyassessgonadalfunction. 17 patients.Dataregardingpituitaryhormonedeficienciesweremissingin6patients(GH5patients,FSH/LH1patient,TSHanteriorPH Data regardingvisualacuitydisordersandfielddefectsweremissingin1629patientsrespectively. Weight statuscouldnotbedeterminedin Cardio- and/orcerebrovascularevents Secondary neoplasms ADH TSH ACTH FSH/LH GH Pituitary hormonedeficiencies: Obstructive sleepapnoea decades resulted in similar overall survival ( decades resultedinsimilar overallsurvival treatmentinmorerecent Initial craniopharyngioma recurrence/progression ( craniopharyngioma comparedwithpatientswithout lower overallsurvival recurrence/progression experienced asignificantly Patientswithcraniopharyngioma craniopharyngioma. similar in patients with childhood- and adult-onset were Overall and recurrence-/progression-free survival compared withtheothertreatmentapproaches ( treatmentwith cyst aspiration craniopharyngioma afterinitial lower recurrence-/progression-freesurvival corrected was not( progression-free survival cyst aspirationand Table 3
n Secondary neoplasmsincludedmeningioma(
= Clinical Study Overweight (25.0–29.9) Normal weight(18.5–24.9) Underweight ( Complete PH Anterior PH Class I–IIIobesity( Class IIIobesity( Class IIobesity(35.0–39.9) Class Iobesity(30.0–34.9) 1), osteomaoftheskull( n
= 1), lungcancer( Long-term healthconditionsinpatientswithcraniopharyngioma. post hoc n
= 2), cavernoussinusschwannoma( < 18.5) ≥ 40.0) ≥ * 90 30.0) analysesrevealedasignificantly n Yttrium brachytherapy, recurrence-/ ) msteim ( mesothelioma =1), n 2 ) heagoa ( haemangioma =1), )) M Wijnenandothers n P
= .3. Bonferroni- =0.03). n 2), prostatecancer(
= n 1), bladdercancer(
= n
1), Hodgkinlymphoma( = 1), growthhormone-producingpituitaryadenoma( P .0 for =0.50 P P
=0.01). < 0.01). n
= n
2), breastcancer( = 1), ovariancancer( All craniopharyngiomas n brain structures( itself(tumour invadingvital to thecraniopharyngioma In fivepatients(23%)thecauseofdeathwasdirectlyrelated recurrence/progression ( time in the subgroup of patientswith craniopharyngioma ( trend) andlowerrecurrence-/progression-freesurvival Deaths directly related to the craniopharyngioma itself Deaths directlyrelatedtothe craniopharyngioma The cause of death was unknown in six patients (27%). infarction ( ( itself(infection( craniopharyngioma patients (50%)diedofcausesnotdirectlyrelatedtothe
Sequelae ofcraniopharyngioma = P n 116 (91) 111 (87) 110 (92) 125 (98) 1) andneuro-endocrinetumouroftheappendix(
11 (9) 62 (56) 17 (15) 11 (10) 34 (31) 27 (24) 18 (16) 50 (39) 24 (19) 36 (28) 11 (9) 19 (15) 30 (23) 30 (23) 65 (66) 71 (63) 37 (21–54) 13 (5–23) 20 (16) 22 (17) 63 (50) 85 (70) 78 (61) 99 (81) < = 4 (4)
2), secondary malignancies( 2), secondary
0.01 for trend). Overall survival wasalso similarover 0.01 fortrend).Overallsurvival In ourstudy, 22patients(17%)diedduring follow-up. 128 n
= n 2), arachnoidcyst(
= n 1), cervicalcancer(
= 1), radiationencephalopathy ( n
Childhood-onset = 4), brainherniation( 37 (64) 14 (24) 18 (31) 10 (17) 35 (56) 12 (19) 22 (35) 10 (16) 16 (25) 20 (32) 31 (66) 34 (63) 22 (15–31) 14 (5–23) 41 (66) 48 (79) 50 (79) 58 (92) 54 (86) 49 (91) 57 (93) 61 (97) n 7 (11) 5 (9) 7 (12) 4 (7) 6 (10) 3 (5) 7 (11)
=
P Downloaded fromBioscientifica.com at09/28/202102:26:01PM 1), pinealglandcyst( 63 .6 o trend). for =0.46 n
= 2), thyroglossalductcyst( n
= 1), calcifyingodontogeniccyst n Adult-onset 25 (47) 16 (30) 17 (32) 11 (21) 15 (23) 12 (19) 14 (22) 14 (22) 10 (15) 34 (65) 37 (64) 54 (44–70) 11 (6–23) 17 (26) 15 (23) 22 (34) 37 (61) 28 (43) 58 (91) 57 (88) 61 (94) 42 (68) 64 (99) ) cerebrovascular =3), 4 (6) 3 (6) 6 (11) 0 (0) 5 (8) 9 (14) 176
n ) cric arrest cardiac =4), 65 www.eje-online.org n :6 n =1). ) pancreatic =1), n ). Eleven =1)). P n < < < < < < < -value** =1), 0.01 0.07 0.01 0.03 0.01 0.77 0.74 0.73 0.01 0.62 0.32 0.08 0.01 0.63 0.92 0.07 0.22 0.12 0.01 0.93 0.09 0.71 0.75 0.61 0.03 0.95 0.93 0.01 0.81
n 761 =1)). via freeaccess European Journal of Endocrinology www.eje-online.org after initial craniopharyngioma treatment with grosstotal after initialcraniopharyngioma a similar pattern of long-term health effects observed yearssincepresentation,we a medianfollow-upof13 on afullspectrumoflong-term healthconditions.After cross-sectionally analysedretrospectivelycollecteddata treatedfrom1980 onwards,we craniopharyngioma In thislargesingle-centrestudyofpatientswith Discussion disease ( well as in patients with childhood- and adult-onset aspiration and subtotal resection with or without radiotherapy, cyst treatmentwithgrosstotalresection, craniopharyngioma itself occurredwithsimilarfrequenciesafterinitial and deathsnotdirectlyrelatedtothecraniopharyngioma Epilepsy Visual fielddefects Visual acuitydisorders Age (years)atfollow-up,median(IQR) Follow-up (years),median(IQR) n Table 4 Neurological deficits Mild Severe Cognitive impairment Behavioural changes Psychiatric conditions Weight status (BMI(kg/m
Obstructive sleepapnoea Secondary neoplasms ADH TSH ACTH FSH/LH GH Pituitary hormonedeficiencies: Cardio- and/orcerebrovascularevents w/o, without. IQR, interquartilerange; in 5patients,andcompletePH1patient).Also8patientsweretooyoungtoreliablyassessgonadalfunction. 16 patients.Dataregardingpituitaryhormonedeficienciesweremissingin5patients(GH4patients,FSH/LH1patient,TSHanteriorPH Data regardingvisualacuitydisordersandfielddefectsweremissingin1528patientsrespectively. Weight statuscouldnotbedeterminedin Underweight ( Normal weight(18.5–24.9) Overweight (25.0–29.9) Class Iobesity(30.0–34.9) Class IIobesity(35.0–39.9) Class IIIobesity( Class I–IIIobesity( Complete PH Anterior PH Clinical Study P Long-term healthconditionsaccordingtoinitialcraniopharyngiomatreatment.Datarepresentedas =0.28). < 18.5) ≥ 90 40.0) ≥ Yttrium brachytherapy( 90 30.0) Yttrium, 2 )) 90 Yttrium brachytherapy;BMI,bodymassindex;GTR,grosstotalresection;RTx, radiotherapy;STR,subtotalresection; M Wijnenandothers P .0, as =0.90), 12 (67) 10 (50) 30 (18–51) 14 (6–21) 11 (44) 11 (48) 16 (64) 18 (75) 17 (68) 22 (88) 22 (88) 21 (88) 19 (79) 23 (92) 6 (24) 6 (24) 3 (12) 3 (12) 4 (16) 8 (32) 0 (0) 5 (22) 7 (30) 5 (22) 2 (9) 4 (17) 3 (12) 2 (8) 2 (8)
GTR 25 STR w/oRTx cyst aspirationand resection, subtotalresectionwithorwithoutradiotherapy, ( Dutch generalpopulation,which isestimatedtobe1–4% than the prevalence of obstructive sleep apnoea in the Thisisconsiderablyhigher with craniopharyngioma. frequency ofobstructivesleepapnoea(i.e.9%)inpatients 23 visual disturbancesand27–57%forobesity( hormonedeficiencies, 49–87%for 78–100% forpituitary with otherstudiesthatreportedprevalencerates of health conditionsinourstudy. Thisisin concordance long-term and obesitywerethemostfrequentlyobserved craniopharyngioma. patients withchildhood-comparedadult-onset long-term healthconditionsweremorefrequentin 19 (61) 24 (63) 42 (21–60) 10 (23) 18 (41) 10 (27) 11 (30) 18 (49) 21 (48) 29 (67) 30 (68) 41 (95) 40 (91) 38 (95) 34 (77) 44 (100) 11 (25) Sequelae ofcraniopharyngioma 38 9 (5–23) 8 (18) 6 (14) 2 (5) 7 (16) 9 (21) 3 (8) 6 (16) 2 (5) 5 (14) 5 (11) 8 (18)
, ). Sinceonlypatientswithsuspected sleepdisordered 44 26 Pituitary hormonedeficiencies,visual disturbances Pituitary , 28 , 30 STR withRTx 11 (52) 14 (58) 40 (21–65) 10 (6–14) 14 (61) 12 (48) 19 (76) 13 (52) 22 (88) 22 (88) 22 (92) 20 (80) 25 (100) 3 (12) 5 (20) 3 (12) 2 (8) 9 (36) 7 (28) 9 (36) 1 (4) 4 (17) 4 (17) 8 (35) 3 (13) 3 (13) 1 (4) 6 (24) 4 (16) ,
32 25 ). Notably, arelatively high weobserved 90 Yttrium brachytherapy. Ingeneral, Cyst aspiration Downloaded fromBioscientifica.com at09/28/202102:26:01PM 37 (18–74) 12 (2–24) 5 (71) 5 (71) 2 (25) 1 (13) 1 (13) 0 (0) 2 (25) 2 (25) 5 (63) 0 (0) 1 (13) 2 (25) 2 (25) 2 (25) 5 (63) 1 (13) 1 (13) 3 (38) 4 (50) 4 (50) 6 (75) 6 (75) 6 (86) 5 (63) 7 (88) 1 (13) 2 (25)
8 176 17 (94) 16 (84) 35 (28–56) 22 (9–29) 11 (69) 12 (67) 10 (48) 20 (95) 17 (81) 18 (95) 17 (94) 21 (100) 90 n :6 8 (38) 9 (43) 5 (24) 4 (19) 7 (33) 2 (10) 8 (38) 0 (0) 2 (13) 3 (19) 6 (38) 2 (13) 3 (19) 1 (5) 8 (40) 1 (5) 4 (19)
(%). Yttrium 21 10 , 20 P -value 762 0.07 0.20 0.72 0.13 0.13 0.36 0.25 0.81 0.28 0.11 0.56 0.65 0.28 0.95 0.82 0.82 0.58 0.58 0.98 0.49 0.66 0.38 0.41 0.71 0.46 0.33 0.08 0.71 0.12 0.71 ,
22 via freeaccess ,
European Journal of Endocrinology craniopharyngioma treatmentwithgrosstotalresection craniopharyngioma and lesshypogonadotropic hypogonadism after initial Merchant years ( 122 patients after a median follow-up of 5 subtotal resectionwithorwithoutradiotherapy in treatment withgrosstotalresectioncompared panhypopituitarism after initialcraniopharyngioma ahigherrateofdiabetes insipidusand only observed ( after ameanfollow-upof9 years or subtotalresectionwithradiotherapyin121patients treatmentwithgross totalresection craniopharyngioma subtotal resectionwithoutradiotherapycomparedwith treatmentwith defects afterinitialcraniopharyngioma 9 years ( in123patientsafteramedianfollow-upof neurosurgery treatmentwithout compared withcraniopharyngioma treatment with neurosurgery initial craniopharyngioma ahigherfrequencyofdiabetesinsipidusafter observed treatmentapproaches.Lo craniopharyngioma differences in long-termhealth effects after different initial no important with our results, these studies observed treatment approach( accordingtoinitial in patientswithcraniopharyngioma few otherstudiescomparedlong-termhealthconditions Onlya sleep apnoeainpatientswithcraniopharyngioma. an underestimationoftherealprevalenceobstructive our study, frequencyof9%mayevenbe theobserved breathing wereevaluatedforobstructivesleepapnoeain Percent survival (%) CD Percent survival (%) AB Clinical Study 100 100 25 50 75 25 50 75 0 0 01 01 35 ). Karavitaki t al et Childhood- vsadult-onset Adult-onset Childhood-onset Overall survival . only observed morediabetesinsipidus . onlyobserved 02 02 All patient Years Years et al 17 s , 03 . only observed more visual field . only observed 03 35 , 36 M Wijnenandothers , 0 36 37 0 ). Schoenfeld ). Inconcordance
Percent survival (%) Percent survival (%) 100 100 25 50 75 25 50 75 0 0 01 01 et al According toinitialtreatment no recurrence/progression Recurrence/progression vs . only et al 17 Recurrence/progression No recurrence/progression 90 Cyst aspiration STR withRTx STR w/oRTx GTR Yttrium 02 02 ). . Years Years fe einflo-po 2 years( after amedianfollow-upof 12 patients derivedfromtwo academic centresinFrance compared withadult-onset diseaseinacohortof171 and panhypopituitarismin patientswithchildhood- a significantlyhigherprevalenceofdiabetesinsipidus concordance withourresults,Gautier patients afteramedianfollow-upof6 years( compared withsubtotalresectionradiotherapyin30 and adult-onset craniopharyngioma ( and adult-onset craniopharyngioma health conditionsbetweenpatientswithchildhood- disease ( an importantriskfactorforcardio-andcerebrovascular Aginghasbeen establishedas onset craniopharyngioma. significantly olderageatfollow-upofpatientswithadult- with childhood-onset disease. This may be due to the cerebrovascular eventsinpatientswithadult-compared significantlymorecardio-and contrast, weobserved In patients withadult-onsetcraniopharyngioma. and/or third ventricle involvement compared with tumours associatedwithhydrocephalusandhypothalamic presented moreoftenwithmulticystictumours,aswell study, patientswithchildhood-onsetcraniopharyngioma alreadypresentatdiagnosis.Inour craniopharyngioma between patientswithchildhood-andadult-onset may beexplainedbydifferencesintumourcharacteristics This compared withadult-onsetcraniopharyngioma. to occur more frequently in patients with childhood- Sequelae ofcraniopharyngioma 03 In ourstudy, long-termhealthconditionsseemed 03 39 ). Severalotherstudiescomparedlong-term 0 0 radiotherapy; STR,subtotalresection; GTR, grosstotalresection;RTx, status. (D) According torecurrence/progression and adult-onsetcraniopharyngioma. treatment. (C)Patientswithchildhood- (B) According toinitialcraniopharyngioma craniopharyngioma. (A)Allpatients. Overall survivalinpatientswith Figure 2 w/o, without. Downloaded fromBioscientifica.com at09/28/202102:26:01PM 90 Yttrium, 90 Yttrium brachytherapy; 176 www.eje-online.org :6 28 30 t al et , ). Incontrast, 37 30 . observed . observed ). , 36 763 ). In via freeaccess European Journal of Endocrinology www.eje-online.org adult-onset disease ( were similar between patients with childhood- and hormone deficiencyandpanhypopituitarism pituitary who were followed for a mean 17 years, frequencies of any from theKIMS(PfizerInternational MetabolicDatabase) which included393growthhormone-deficientpatients Intheirstudy,with childhood-onsetcraniopharyngioma. frequency ofobesityinpatientswithadult-compared Kendall-Taylor STR, subtotalresection;w/o,without. brachytherapy; GTR,grosstotalresection;RTx, radiotherapy; and adult-onsetcraniopharyngioma. craniopharyngioma treatment.(C)Patientswithchildhood- craniopharyngioma. (A)Allpatients.(B)Accordingtoinitial Recurrence-/progression-free survivalinpatientswith Figure 3 C Percent survival (%) Percent survival (%) B Percent survival (%) A Clinical Study 100 100 100 25 50 75 25 50 75 25 50 75 0 0 0 Recurrence-/progression-free survival 01 01 01 According toinitialtreatment Childhood- vsadult-onset 02 t al et 02 02 All patients Y ears Y Y 28 . observed asignificantlyhigher . observed ears ears ). The aforementioned study by 03 03 03 M Wijnenandothers 90 Yttrium, 0 0 0 90 Yttrium Adult-onset Childhood-onset 90 Cyst aspiration STR withRT STR w/oRT GTR Yttrium x x between 40–95%and44–76%respectively( ratesoverall andrecurrence-/progression-freesurvival thatreported10-yearpatients withcraniopharyngioma respectively. Thisiscomparabletootherstudiesin treatmentof85%and74%craniopharyngioma ratesafterinitialprogression-free survival craniopharyngioma ( which wasmorecommoninpatientswithadult-onset for completedependencyactivitiesofdailyliving, except childhood- andadult-onsetcraniopharyngioma, in long-termhealthconditionsbetweenpatientswith Karavitaki lower after initial craniopharyngioma treatmentwithlower afterinitialcraniopharyngioma wassignificantlyrecurrence-/progression-free survival cyst aspirationand resection, subtotalresectionwithorwithoutradiotherapy, treatment with grosstotalinitial craniopharyngioma 23 (e.g. hypopituitarismand hypothalamic dysfunction), term healthconditionscaused bytumourandtreatment diseases ( pituitary mortality riskcompared with patientsother seem to have an increasedwith craniopharyngioma ( onset craniopharyngioma in patients with adult- compared with childhood- by Rao results ( similar Other studies observed craniopharyngioma. comparable inpatientswithchildhood-andadult-onset wereoverall andrecurrence-/progression-freesurvival subtotal resectionwithradiotherapy( radiotherapy comparedwithgrosstotalresectionor was significantlyloweraftersubtotalresectionwithout United StatesNationalCancerDatabase.Overallsurvival registeredinthe697 patientswithcraniopharyngioma study byRao or subtotalresectionwithradiotherapy( without radiotherapycomparedwithgrosstotalresection treatmentwithsubtotalresectioncraniopharyngioma was significantly lower after initialfree survival radiotherapy. However, recurrence-/progression- total resectionandsubtotalwithorwithout treatment with grossafter initialcraniopharyngioma by Karavitaki treatment approach ( accordingtoinitialpatients withcraniopharyngioma inoverall andrecurrence-/progression-freesurvival approaches. Two otherstudiesalsoinvestigated cyst aspirationcomparedwiththeothertherapeutic Sequelae ofcraniopharyngioma , 24 We 10-yearoverallandrecurrence-/ observed , 25 et al 24 ). Inourstudy, wassimilarafter overallsurvival et al , . observed significantlyloweroverallsurvival . observed 30 et al , . did not observe anysignificantdifferences . didnotobserve t al et 36 . investigated 5-year overall survival in. investigated5-yearoverallsurvival ). However, the aforementioned study 21 . observed similaroverall survival . observed 90 36 34 ). Thismightberelatedto long- Yttrium brachytherapy. However, ). , Downloaded fromBioscientifica.com at09/28/202102:26:01PM 36 ). The aforementioned study 34 ). Interestingly, patients 176 34 :6 ). Inourstudy, 36 ). Arecent 10 , 21 764 , 22 via freeaccess , European Journal of Endocrinology be interpretedwithcaution, ascognitiveimpairments neurocognitive andneuropsychological sequelaeshould earlier decades.Furthermore, ourresultsonlong-term resection,especiallyduringof craniopharyngioma This mayhavebiasedthe assessmentofthedegree sensitive earlier compared with more recent decades. future. Inaddition,neuroimagingtechniqueswereless number ofpatientswillbecomeavailableinthenear with anadequatefollow-updurationandasufficient studiesseems unlikelythatprospectiveobservational adequately studylong-term health conditions,it and theprolongedfollow-updurationrequired to data. However, duetotherarityofcraniopharyngioma collection maypredisposetoselectionbiasandmissing results ofourstudy. Theretrospectivenature ofdata limitations should be considered when interpreting the in theotherstudies).Besidesthesestrengths,some years yearsvs3–12 brachytherapy inourstudy(22 explained byalongerfollow-updurationafter disturbances and51%forobesity).Thismaybe hormonedeficiencies,61–90%forvisualpituitary health effectscomparedwithourstudy(55–90%for reported somewhatlowerfrequenciesoflong-term 90 treatmentwithconditions aftercraniopharyngioma Only afewotherstudiesinvestigatedlong-termhealth ( is noteffectiveforsolidcraniopharyngiomas depth of results incystshrinkage( radiation-induced destructionofepithelialcystlining cysts( isotopes incraniopharyngioma invasive stereotacticapplicationofbeta-emitting 1952 byLeksellandLiden,involvestheminimally- infirst introducedasatreatmentforcraniopharyngioma 90 as therelativelylargenumberofpatientstreatedwith of long-termhealthconditionsinvestigated,aswell more recent decades. in progression inpatientstreatedforcraniopharyngioma asignificantlyhigherriskofrecurrence/ observed treatment inmorerecentdecades.Incontrast,we neurological deficits after initial craniopharyngioma significantly lowerrisksofmorbidobesityandsevere concordance with other studies ( treatment becamelessaggressiveovertime.Thisisin treatment ( andtheirtendencytorecuraftercraniopharyngiomas as well as to the locally aggressive behaviour of Yttrium brachytherapy( Yttrium brachytherapyassessed.Brachytherapywas Clinical Study Strengths of our study include the full spectrum In ourinstitution,initialcraniopharyngioma 90 Yttrium in soft tissue, 21 , 22 ). 41 ). Duetotheshorthalf-value 42 , 90 M Wijnenandothers 43 Yttrium brachytherapy , 4 , 44 20 ). Thesestudies 40 ). We observed ). Subsequent 90 Yttrium 42 ). ). Due tothehighfrequencyofendocrinedisorders, management, bothatdiagnosisandduringfollow-up. regarded as a chronic condition requiring multidisciplinary shouldbe with adult-onsetdisease.Craniopharyngioma affected bylong-termhealthconditionsthanpatients aregenerallymore childhood-onset craniopharyngioma result incomparablelong-termhealtheffects.Patientswith radiotherapy, cystaspirationand gross totalresection,subtotalresectionwithorwithout Initial are frequentinpatientswithcraniopharyngioma. rates,long-termhealthconditions encouraging survival minority ofpatients. since these data were only available in aor papillary), (i.e.adamantinomatoussubtype ofcraniopharyngioma long-term healthconditionsaccording to histological formally tested.Moreover, wewereunabletocompare if documentedin the patient files and havenot been and behaviouralchangeswereconsideredpresent References and follow-upcareofourpatients. The authorswouldliketothankthephysiciansinvolvedintreatment Acknowledgements the public,commercialornot-for-profit sector. This researchdidnotreceiveanyspecificgrantfromfundingagencyin Funding perceived asprejudicingtheimpartialityofthisstudy. The authorsdeclarethatthereisnoconflictofinterestcouldbe Declaration ofinterest long-term tumour-andtreatment-relatedmorbidity. well asontherapeuticstrategiesthataimtoreducethe modifiable riskfactorsforlong-termhealthconditions,as shouldfocuson Future studiesoncraniopharyngioma and follow-upcareofpatientswithcraniopharyngioma. endocrinologists shouldplayapivotalroleintheprimary Sequelae ofcraniopharyngioma 2 4 3 1 2013 bf01939537) ausgehend. 011-0540-6) ofNeuro-Oncology Journal inchildrenand adults. world incidenceofcraniopharyngioma inDenmark( Incidence ofcraniopharyngioma J, JorgensenJO,BjerreP, Andersen M,AndersenC,JorgensenJ (doi:10.1210/er.2013-1115) Barkhoudarian G & Laws ER. Craniopharyngioma: history.Barkhoudarian G&LawsER.Craniopharyngioma: Von ZenkerAF. EnormeZystenbildungimGehirn,vomHirnanhang Nielsen EH,Feldt-RasmussenU,PoulsgaardL,KristensenLO,Astrup Muller HL.Craniopharyngioma. In conclusion,ourstudydemonstratesthatdespite 16 1–8. Virchows Archiv (doi:10.1007/s11102-012-0402-z) 2011 1857 Downloaded fromBioscientifica.com at09/28/202102:26:01PM 104 Endocrine Reviews 2 454–466. 755–763. 90 Yttrium brachytherapy 176 (doi:10.1007/ (doi:10.1007/s11060- n www.eje-online.org :6 8) n estimated and =189) 2014 35 513–543. Pituitary 765 et al via freeaccess
. European Journal of Endocrinology 10 20 18 17 16 15 14 13 12 11 www.eje-online.org 19 9 8 7 6 5 Clinical Study Du C,FengCY, Yuan XR,LiuQ,PengZF, JiangXJ,LiXiaoGL, Tan TS,PatelL,Gopal-KothandapaniJS,EhtishamS,Ikazoboh Schubert T, Trippel M,Tacke U,vanVelthoven V, GumppV, Bartelt Schoenfeld A,PekmezciM,BarnesMJ,Tihan T, GuptaN, Winkfield KM, Tsai HK, Yao X,LarsonE,Neuberg D,PomeroySL, Morisako H,GotoT, GotoH,BohounCA,Tamrakar S&Ohata Moussazadeh N,PrabhuV, BanderED,CusicRC, Tsiouris AJ,Anand Cheng J,ShaoQ,PanZ&You J.Analysisandlong-termfollow-up Xing H,HuiP&Yang B.Removalofcraniopharyngioma Bal E,OgeK&BerkerM.Endoscopicendonasaltranssphenoidal Puget S,GarnettM,Wray A,GrillJ,HabrandJL,BodaertN, resection of craniopharyngiomas: acase-matchedsingle-institution resection ofcraniopharyngiomas: VK &SchwartzTH.Endoscopicendonasalversusopentranscranial SCS.0000000000003176) ofCraniofacialSurgery Journal of thesurgicaltreatmentchildrenwithcraniopharyngioma. 147–149. via fronto-basalinterhemisphericapproach. 2016 nineyearsofexperience. craniopharyngiomas: surgery, andrecurrent/residual areliablemethodfortreatingprimary (doi:10.1016/j.wneu.2016.03.002) of 177continuouscases. via anunilateralsubfrontalapproach–aretrospectivestudy YF &XiongT. Microsurgicalmanagementofcraniopharyngiomas Neurosurgery the surgicalapproachesandhypothalamicprotection. withspecialreferenceto of 202pediatriccraniopharyngiomas 2010 neuroendocrine sequelae of paediatric craniopharyngioma: a40 neuroendocrine sequelaeofpaediatric craniopharyngioma: EC, HaywardR,AquilinaK,SkaeM, ThorpN,PizerB 106 islessmore? childhood craniopharyngiomas: S, OstertagC&NikkhahG.Neurosurgicaltreatmentstrategiesin (doi:10.1007/s11060-012-0806-7) craniopharyngiomas. resectionandadjuvantradiation for superiority ofconservative Lamborn KR,BanerjeeA,MuellerS,ChangBergerMS pbc.22884) Pediatric BloodandCancer outcomes followingtreatmentofchildhoodcraniopharyngioma. Ullrich NJ,CohenLE,KieranMW, ScottRM 016.9.FOCUS16211) craniopharyngiomas. basedonananatomicalsubclassificationof K. Aggressivesurgery CUS16299) analysis. degree ofhypothalamicinvolvement. classificationandtreatmentaccordingtothe craniopharyngiomas: Zerah M,BezerraRenierD,Pierre-KahnA 2009 in86children. craniopharyngiomas andrecurrent JH. Efficacyandsafetyofradicalresectionprimary 1350–1359. term resultsinalargecaseseries. inadultsandchildren:earlylong- of craniopharyngioma D, Weber G,ChiumelloG&GiovanelliM.Neurosurgicaltreatment 012-0414-8) craniopharyngioma. 013-0050-9) Endocrinological Investigation Zhang YQ,MaZY, Wu ZB,LuoSQ&Wang ZC.Radicalresection Elliott RE,HsiehK,HochmT, Belitskaya-LevyI,Wisoff J&Wisoff Mortini P, LosaM,PozzobonG,BarzaghiR,RivaAcernoS,Angius for Buchfelder M,SchlafferSM,LinF&KleindienstA.Surgery Karavitaki N.Managementofcraniopharyngiomas. 3–12. 25 94 5 30–48. 1419–1427. 375–385. Neurosurgical Focus (doi:10.3892/ol.2016.4555) (doi:10.3171/ped.2007.106.1.3) 2008 (doi:10.3171/2010.11.JNS10670) (doi:10.3171/2009.7.PEDS09215) 44 (doi:10.1016/j.wneu.2016.07.004) 435–443. Pituitary (doi:10.1007/s00381-009-0978-4) Journal ofNeuro-Oncology Journal Neurosurgical Focus World Neurosurgery 2011 2016 2014 2016 2013 (doi:10.1159/000172965) 56 Journal ofNeurosurgery Journal 41 37 1120–1126. 27 16 E7. Journal of Neurosurgery Pediatrics ofNeurosurgery Journal 219–228. e763–e766. 18–25. Journal ofNeurosurgery Journal M Wijnenandothers 2016 (doi:10.3171/2016.9.FO 2016 et al Oncology Letters et al (doi:10.1007/s11102- Child’s System Nervous 2012 41 (doi:10.1002/ (doi:10.1007/s40618- World Neurosurgery . Long-termclinical . Pediatric E10. 90 (doi:10.1097/ Journal of Journal 454–468. 108 et al Pediatric (doi:10.3171/2 2011 et al 133–139. . The 2016 2007 . The 114
12
34 33 32 31 26 25 24 23 22 21 30 29 28 27 Sequelae ofcraniopharyngioma Rao YJ,HassanzadehC,Fischer-Valuck B,ChicoineMR,KimAH, Smith TR,CoteDJ,JaneJAJr&LawsERJr. Physiologicalgrowth Muller HL,BuebK,BartelsU,RothC,HarzGrafN,Korinthenberg Wijnen M,OlssonDS,vandenHeuvel-EibrinkMM,Wallenius V, Elliott RE,JaneJAJr&Wisoff JH.Surgical managementof Hoffmann A,Warmuth-Metz M,LohleK,ReichelJ,Daubenbuchel Pan J,QiS,LiuY, LuY, PengJ,ZhangX,XuY, HuangGL&Fan J. Lee CC,Yang HC,ChenCJ,HungYC,Wu HM,ShiauCY, Guo IL,NilssonAG&JohannssonG. Olsson DS,AnderssonE,Bryngelsson Sherlock M,Ayuk J,Tomlinson JW, Toogood AA,Aragon-AlonsoA, Gautier A,GodboutGroshenyC,Tejedor I,CoudertM,Courtillot Sterkenburg AS,HoffmannA,GebhardtU,Warmuth-Metz M, Kendall-Taylor P, JonssonPJ,AbsR,ErfurthEM,Koltowska-Haggstrom Honegger J,BuchfelderM&FahlbuschR.Surgicaltreatmentof patients with Craniopharyngioma inthenationalcancerdatabase. patients withCraniopharyngioma Perkins SM&HuangJ.Patternsofcare andtreatmentoutcomesof Pediatrics Genentech NationalCooperativeGrowth Study. the hormone replacementandrateofrecurrence ofcraniopharyngioma: (doi:10.1055/s-2001-16855) factors andqualityoflife. –Germanmulticenterstudyonpre-operative risk craniopharyngioma R, BettendorfM,KuhlJ,GutjahrP (doi:10.1038/ijo.2016.195) years offollow-up. related hypothalamicobesity-Amatchedcase-controlstudywithtwo forcraniopharyngioma- S. Efficacyandsafetyofbariatricsurgery Janssen J,DelhantyPJ,vanderLelyAJ,JohannssonG&Neggers and Metabolism systematic analysisof171patients. a of recurrenceandlong-termmorbidityincraniopharyngioma: 422–428. study onincidenceandlong-termoutcome. multicenter inchildhood-onsetcraniopharyngioma: carotid artery AM, SterkenburgAS&MullerHL.Fusiformdilatationoftheinternal (doi:10.3171/2015.7.PEDS14449) patients. clinicalanalysisof226 Growth patternsofcraniopharyngiomas: (doi:10.3171/2014.8.GKS141411) Neurosurgery reportona20-yearexperience. craniopharyngioma: WY, for PanDH,ChungWY&LiuKD.GammaKnifesurgery 467–474. in Sweden. especially inpatientswithchildhoodonset:apopulation-basedstudy Excess mortalityandmorbidityinpatientswithcraniopharyngioma, er.2009-0033) disease. pituitary Sheppard MC,BatesAS&StewartPM.Mortalityinpatientswith ofEndocrinology Journal C, JublancDeKerdanetM,PoirierJY, RiffaudL Oncology newlyreportedlong-termoutcomes. craniopharyngioma: and neuropsychological/psychosocialstatusafterchildhood-onset hypothalamicobesity,Daubenbuchel AM&MullerHL.Survival, eje.1.01877) ofEndocrinology European Journal comparedwithadult-onsetcraniopharyngioma. craniopharyngioma features andthequalityoflifeinadultswithchildhood-onset M, PriceDA&Verhelst J.Theclinical,metabolicandendocrine 1999 endocrinologicalresults. craniopharyngiomas: 630–643; discussion643. transcranial andtranssphenoidalapproaches. inchildren:meta-analysisandcomparisonof craniopharyngiomas year meta-dataanalysisof185casesfromthreeUKcentres. 90 251–257. 2015 2016 Journal of Neurosurgery Pediatrics ofNeurosurgery Journal (doi:10.1007/s11102-016-0722-5) (doi:10.1210/jc.2014-3525) Journal ofClinicalEndocrinologyand Metabolism Journal 2014 18 17 2012 408–412. 1029–1038. Endocrine Reviews 121 (doi:10.3171/jns.1999.90.2.0251) International Journal ofObesity Journal International 97 (Supplement)167–178. 2017 1258–1267. (doi:10.1227/NEU.0b013e31821a872d) Klinische Pädiatrie (doi:10.3171/2016.4.PEDS16112) Downloaded fromBioscientifica.com at09/28/202102:26:01PM 176 (doi:10.1093/neuonc/nov044) 2005 359–369. 2010 et al Journal ofClinicalEndocrinology Journal (doi:10.1210/jc.2011-2817) 152 . Obesityafterchildhood 31 2016 557–567. 301–342. (doi:10.1530/EJE-16-0812) 2001 176 Pituitary Neurosurgery
17 Journal ofNeurosurgery Journal Journal of Neurosurgery ofNeurosurgery Journal :6 2016 418–433. 213 et al (doi:10.1530/ Journal of Journal 2016 (doi:10.1210/ 244–249. . Markers 41 210–216. 2015 2011 Neuro- 19 European
766 100 69
via freeaccess
European Journal of Endocrinology 38 37 36 35 Clinical Study Damen-van BeekZ,LucassenPL,GorgelsW, SmeltAF, Knuistingh Merchant TE,KiehnaEN,SanfordRA,MulhernRK,ThompsonSJ, Karavitaki N,BrufaniC,Warner JT, AdamsCB,RichardsP, Ansorge Lo AC,HowardAF, NicholA,SidhuK,AbdulsatarF, HasanH& A8679. sleeping pills’. Neven A&BoumaM.TheNHGguideline‘sleepproblemsand (doi:10.1016/S0360-3016(02)02799-2) ofRadiationOncology,Journal Biology, Physics Children’s Research Hospitalexperience1984–2001. Wilson MW, theSt.Jude LustigRH&KunLE.Craniopharyngioma: 2265.2005.02231.x) Clinical Endocrinology and adults:systematicanalysisof121caseswithlong-termfollow-up. O, ShineB,Turner HE&Wass inchildren JA.Craniopharyngiomas 1011–1018. ofRadiationOncology, Journal International Biology, Physics theBritishColumbiacanceragencyexperience. craniopharyngioma: Goddard K.Long-termoutcomesandcomplicationsinpatientswith 016-2342-3) ofNeuro-Oncology Journal (doi:10.1016/j.ijrobp.2014.01.019) Nederlands Tijdschrift voorGeneeskunde 2005 2016 62 397–409. 132 109–117. M Wijnenandothers (doi:10.1111/j.1365- 2002 (doi:10.1007/s11060- 53 533–542. 2015 International International 2014 159 88
Revised versionreceived16March2017 Received 19January2017 Accepted 21March2017 44 43 42 41 40 39 Sequelae ofcraniopharyngioma Julow JV. Intracysticirradiationforcraniopharyngiomas. Voges J,SturmV, LehrkeR,Treuer H,GaussC&BertholdF. Cystic Van denBergeJH,BlaauwG,BreemanWA, RahmyA&Wijngaarde R. Szeifert GT, BalintK,SiposL,SarkerMH,CzirjakS&Julow Leksell L&LidenK.Atherapeutictrialwithradioactiveisotopesin Sniderman AD&FurbergCD.Ageasamodifiableriskfactorfor 2013 (doi:10.1097/00006123-199702000-00006) sources. with stereotacticallyappliedcolloidalbeta-emittingradioactive irradiation long-termresultsafterintracavitary craniopharyngioma: Neurosurgery brachytherapyofcysticcraniopharyngiomas. Intracavitary (doi:10.1159/000100173) isotope. irradiationwithyttrium-90after stereotacticintracavitary J. Pathologicalfindingsincysticcraniopharyngiomas Physiological Applications cystic braintumour. In S0140-6736(08)60313-X) cardiovascular disease. 16 34–45. Neurosurgery Progress inNeurological Surgery 1992 (doi:10.1007/s11102-012-0442-4) 77 1997 545–550. Lancet Radioisotope Techniques, Volume 1:Medicaland . pp. 1–4 Oxford: HM Stationary Office1952. . pp.1–4Oxford:HMStationary 40 Downloaded fromBioscientifica.com at09/28/202102:26:01PM 2008 263–269;discussion269–270. (doi:10.3171/jns.1992.77.4.0545) 371 2007 1547–1549. 176 20 www.eje-online.org :6 297–302. (doi:10.1016/ Pituitary Journal of Journal 767 via freeaccess