ProjectProposalforConsortium

VolumetricResponseofCysticVestibularSchwannomastoRadiosurgery

GregBowden,L.DadeLunsford,MD.1,3

DepartmentsofNeurologicalSurgery1,andtheCenterforImage-GuidedNeurosurgery3,Pittsburgh,PA.

INTRODUCTION

Gammaknife®stereotacticradiosurgeryisavaluableprimarymanagement

modalityforVS.Asignificantdebatehassurroundedtheriskbenefitratioofvarious

managementparadigms(surveillance,microsurgeryandradiosurgery),particularly

inrelationtotumorvolumeandcysticcharacteristics.Unfortunately,thereremains

adearthofinformationregardingtheimportanceofcontrastenhancedimaging

characteristicsespeciallytherecognitionofintratumoralcysticchangesontumor

regressionandcontrolrates.Thisstudypresentstheclinicalandvolumetric

outcomesforVStumorswithandwithoutintratumoralcysticchanges.

Objective

Wehypothesizethattumorswithradiographicevidenceofcysticformation

willhaveagreatervolumetricresponsetoSRS.Inthisstudywewillcorrelatethe

radiographicappearanceofVSbeforeradiosurgerywiththedelayedvolumetric

responseandtheassociatedoutcomes.

MATERIALSandMETHODS

PatientCharacteristics

AmultiinstitutionretrospectiveanalysisofvolumetricresponsestoVSafter

Gammaknife®SRS.Patientswillbecollectedduringa10yearperiodbetween

January1st,2003andDecember31st,2012.Patientswhomeetthefollowing

inclusioncriteriawillbeanalyzed:nopriorsurgicalorradiationprocedures,an

extracanalicularvolumegreaterthan0.7cm3,NF2negativeanddocumented

imagingfollow-up.

Tumorcharacteristics

PatientswillbesubdividedbasedonT1+GadoliniumandT2MRIcharacteristics

into3groupsbased:macrocystictumors(intratumoralcysticregions:T1-

hypointensityandT2-hyperintensity),microcyticchanges(intratumoralcystic

regions:T1-hypointensityandT2-hypointensity),andhomogeneouslycontrast

enhancingtumorswithoutcysticchanges(Fig.1.).Theextracanalicularvolumes

willbecalculatedbasedonhigh-resolutionT1-weightedgadoliniumenhanced

magneticresonanceimaging(MRI.Ateachdatapointtumorvolumeswillbe

calculatedbasedontheformula!!𝑋 𝑙𝑒𝑛𝑔𝑡ℎ 𝑌 𝑤𝑖𝑑𝑡ℎ 𝑍 ℎ𝑒𝑖𝑔ℎ𝑡 ofthe

extracanalicuarportionofthetumor.

Audiometry&FacialFunction

AllpatientsthathaveformalaudiometryconductedpriortoandpostSRS,

willbecollected.Toallowanalysisofhearingoutcomes(speechdiscrimination)in

relationtotheradiographicgroups.TheHouse-Brackman,trigeminalsymptomsand

balancewillalsoberecordedduringthefollow-up.

Statisticalanalysis

Statisticalanalysiswillbeconductedutilizingpropensitymatching,Kaplan-

Meier,andcoxregressionmethodswhereappropriate.

SUPPORTINGEVIDENCE

AUniversityofPittsburghsingleinstitutionretrospectiveanalysisis

currentlyunderreviewbytheNeurosurgeryJournal.Thisstudyincluded219VS

patients,whichaccountedfor42contrastenhancingmacrocystictumors,45

contrastenhancingmicrocystictumors,and132tumorswerehomogeneously

enhancingwithnointratumoralcystformation.Themedianfollow-upwas49.1

months.Themediantumorvolumewas2.6cm3(0.70-16.1cm3)andthemediandose

was12.5Gy(11-13Gy).

Avolumetricreductionof>20%occurredin85.4%ofmacrocystictumors,

76.1%ofmicrocystictumorsand62.8%ofhomogeneouslyenhancingVS.The

medianvolumedecreaseperyearformacrocystic,microcysticandhomogenous

tumorswas17.2%,7.5%and7.9%peryearrespectively(p<0.001)(Fig2.).A2:1

blindedvolumetriccasematchalsoshowedasignificantsizereductionin

macrocystictumorscomparedtonon-cystictumors(p=0.007).Serviceablehearing

wasmaintainedin61.5%ofpatientsthathadGardner-Robertsongrade1or2

hearingpriortotreatment.Surgicalresectionorrepeatradiosurgerywasperformed

in8patients(3.6%)whohadsustainedtumorprogression.

SRSprovidedVStumorcontrolin>95%ofpatients,regardlessof

radiographiccharacteristics.Tumorvolumeregressionwasmostevidentinpatients

withcystictumors.

PublicationGoals

1) Eliminatethemisconceptionthatcysticchangesareanegativepredictoroftumor

responsetoSRS

2) Demonstrateclearvolumetricchangeswithinandbetweenradiographicallydistinct

VStumorsubsets.

3) Determineassociatedneurologicaloutcomesandwhetherradiographicallydistinct

tumorshavedifferingimpactsonfunctionaftertreatment.

4) Builduponapreviousstudytoincreaseevidenceandstatisticalpower.

Pleasefindaspreadsheetincludingexamplepatientsattached.

Yoursupportinthisclinicalstudyisgreatlyappreciated,

AnyquestionsorconcernscanbedirectedtoDr.GregBowden.

Sincerely,

GregBowdenM.D,MSc,FRCSC

UniversityofPittsburgh

bowdeng@upmc.edu

FIGURESANDTABLESFigure1.VestibularschwannomamagneticresonanceimagingatthetimeofSRS:A)HomogenousSPGR,B)HomogenousT2,C)MicrocyticSPGR,D)MicrocyticT2,E)MacrocysticSPGRandF)MacrocysticT2.A B

C D

`E F

Figure3.Medianvolumetricdecrease(Percentageofinitialvolume)overtimeforVestibularSchwannomasthatareHomogeneous(square),microcytic(triangle)ormacrocystic(circle).Timeintervalsare:timeofSRS,<1year,1-2years,2-4years,4-6years,and>6years.