听瘤42018年9月5日NF2型相关听神经瘤的诊治策略.ppt

Clinicaloutcomeofneurofibromatosistype2-relatedvestibularschwannoma:treatmentstrategiesandchallenges,浙江大学医学院附属邵逸夫医院神经外科郭洪彬,Themostdifficultis,Whatcausesacousticneuroma,Neurofibromatosis(NF2),NF2,ageneticdisorder,occurswithafrequencyof1in30,000to1in50,000births.Thehallmarkofthisdisorderisbilateralacousticneuromas(anacousticneuromaonbothsides).Thiscreatestheperplexingproblemofthepossibilityofcompletedeafnessifthetumorsarelefttogrowunchecked.,Introduction,Neurofibromatosistype2(NF2)isanautosomaldominantmultipleneoplasiasyndromethatresultsfromamutationinNF2tumorsuppressorgeneonchromosome22q122神经纤维瘤病2型是一种常染色体显性遗传的多发性肿瘤综合征。是由染色体22q12-2突变所致。,AdistinctivefeatureofNF2isbilateralvestibularschwannomas(VSs)withameanageofdiagnosisof25yearsNF2的一个区别性特征是双侧的前庭神经鞘瘤，诊断时平均年龄为25岁。,4例耳,12例耳,8例耳,8例耳,Discussion,NF2isadevastatingdiseasewithmultipleintracranialandextracranialtumors24.ThegrowthpatternofNF2-relatedVSscanbevarious.However,someshowsaltatorypatternafteraquiescentperiod5.NF2是一种破坏性强的多发性的颅内颅外肿瘤。NF2相关的VS的生长模式多种多样。有时是在一段静止期后接着爆发性生长。,OutcomeaftertreatingVSofpatientswithNF2isusuallyworsethanthatofsporadicVSresultingfromaggressivegrowthpattern.CarefulobservationismandatoryforNF2-relatedVSpatientsbecausegrowthpatternisusuallyunpredictable.Inaddition,thehearingstatusmaybecomeabruptlyaggravated.NF2相关的前庭神经鞘瘤的预后比散发的前庭神经鞘瘤的差，原因就是它有时表现为进展极快的生长模式。密切的观察随访是必须的，因为它的生长模式不可预测。而且，患者的听力可能急剧恶化。,MicrosurgicalresectionwasthestandardtreatmentforVSinNF2patients.However,consideringthequalityoflifeincludingpreservationofhearingfunction,surgeryalonemaynotbesuitableforlong-termmanagementofpatients。显微手术切除术是治疗NF2相关的前庭神经鞘瘤的标准治疗。但是，鉴于对患者生活质量和听力保存的考虑，从长期病情管理的角度来说，单纯手术也许并不适合。,performedinrelativelylargersizedtumorsthantumorsthats-GKSperformedin,hearingpreservationrateinf-GKSwaspoorerthanthatofs-GKS.GKS,includingfractionatedGKS,mightberelativelyefficientinlocalcontrolofpatientswithsmall-sizedtumorandserviceablehearing.分次伽马刀治疗的组的肿瘤体积比单次伽马刀治疗组的大，可以解释分次伽马刀治疗组的听力保留的结果为什么比单次伽马刀组的差。伽马刀组，包括分次和单次的，在对于小体积肿瘤病人的听力保留方面，可能相对有效。However,wecouldnotregarditasanabsolutetreatmentmodalityinthatthehearingstatuseventuallydeterioratedinmanycases.Therefore,radiosurgeryshouldbecarefullyconsideredforselectedpatientswithNF2但是我们也不能把伽马刀治疗看做是绝对好的治疗方式，因为很多患者听力状态最终恶化了。因此，选择放射治疗时也应慎重。,Themostimportantfactortodetermineoptimaltimeofinterventionisthemaintenanceofhearingatleastinoneear.Thus,annualMRIscanandaudiometricexaminationaremandatory.Iftheirhearingstartstodeteriorateorthetumorsizestarttoincrease,hearingpreservationsurgery(HPS)shouldbeattempted.选择治疗干预时机的一个重要的考虑因素是保留至少一只耳朵的听力。因此，进行每年的MRI平扫和听力检查是必须的。如果患者的听力开始恶化，或者肿瘤开始增大，听力保留手术应该被考虑进行。,Ifonlyothercuremethods?,techniquessuchascochlearimplants(CIs)andauditorybrainstemimplants(ABIs)canbeconsideredtoaccommodateusefulhearing.Ifhearingcouldnotbepreservedbutwithcochlearnerveactionpotential(CNAP)duringrespectivesurgery,thenCIcanbeimplantedatthetimeofsurgery.However,ifCNAPcouldnotbeobserved,ABIisrecommendedinstead。人工电子耳蜗技术和脑干听觉植入技术可以被考虑用于保留听力。如果手术中，听力无法保留，但耳蜗神经动作电位尚存，可以在术中植入人工电子耳蜗。如果耳蜗动作电位也观察不到，那么ABI脑干听觉植入装置应被推荐使用。,同侧耳的听力3看对侧耳的听力耳的听力3看耳的听力,1，看肿瘤大小。2，看同侧听力。3，看对侧听力。,NF2:bevacizumab-VEGFblockade(贝伐单抗-VEGF阻断剂),ImmunohistochemistryshowsVEGFexpressioninallvestibularschwannomasandVEGFreceptor2expressionin32%ofthetumorvessels.免疫组化显示，血管内皮生长因子（vascularendothelialgrowthfactor，VEGF）在所有听瘤上表达。VEGFreceptor2在32%的听瘤血管上表达。VEGFblockadeimproveshearinginsomepatientswithneurofibromatosistype2(NF2)andisassociatedwithareductionintumorvolumeinmostgrowingvestibularschwannomas.VEGF受体阻滞剂提高一部分NF2患者的听力，伴随大部分的前庭神经鞘瘤的体积缩小。,Afterbevacizumabtreatmentofthese10tumors,9tumorsshrankand6tumorsshowedaresponseonimaging,whichwasmaintainedin4tumorsduring11to16monthsoffollow-up.10例接受贝伐单抗治疗的患者中，9例的肿瘤缩小，6例在影像学上有反应表现，其中的4例在之后的11至16个月的随访时间内维持。Overall,treatmentwaswelltoleratedandwasnotdiscontinuedinanypatientsbecauseofsideeffects.所有的患者都能耐受这种治疗，没有一例因副作用而停止治疗。,Themediantimetoresponseforbothvolumetricreductionandhearingimprovementwas3months.肿瘤体积缩小和听力提高的平均起效时间为3个月。furthermore,theonlypredictive,clinicalmarkerwasthemeanapparentdiffusioncoefficientvalue,aradiologicmarkerofvasogenicedema.而且，临床上唯一的一个预测指标是表观弥散系数值，也是一个反应血管源性脑水肿的放射指标。,Discontinuationofbevacizumabwaslinkedtoanincreaseintumorvolumeandadeclineinhearinginsomepatients.停用贝伐单抗后，一些患者的肿瘤体积缩小，听力下降。Theoptimalduratio