卵巢癌的诊断和治疗医大讲课.ppt

DiagnosisandTreatmentofOvarianCancer,ShenKengDepartmentofOB/GYNPekingUnionMedicalCollegeHospital,EpidemiologyandGeneticFactors,Ovariancanceristhesecondmostcommongynecologicalmalignancy,butthecommonestmalignancyofthefemalegenitaltracttoresultindeathIncidence:Ingeneralpopulationlifetimeriskforovariancancerinawomenisroughly1/70or1.4%.,EpidemiologyandGeneticFactors,TheincidenceinAsia,AfricaandLatinAmericaislowerthaninWesterncountries.Themostcommontumortypeisepithelial(85%).,卵巢癌的危险因素,年龄,危险因素,与子宫内膜、结肠、乳腺癌的关系,家庭史,生产史和激素水平,EpidemiologyandGeneticFactors,Highriskfactors:1.Morethan40yrs.2.Caucasianrace(white)3.Latemenopause.4.Infertility5.PositivefamilyhistoryofCAovary6.BRCAgene,EpidemiologyandGeneticFactors,FamilyhistoryisthestrongestriskfactorforovariancancerWomenwithoneaffectedfirstclassrelative:riskrateforovariancanceris5%Womenwithtwoaffectedfirstclassrelative:riskrateforovariancanceris7%AmemberofHOCS:riskrateforovariancanceris20%-50%BRCA1conservativeresectionpreservefertilityinbilateralborderlinetumoursadjuvanttherapyunprovenUnfavourabletypepoorlydifferentiatedclearcelltumourscapsulepenetrationrupturedcapsulepositivewashingsstageII:standardoperation+adjuvanttherapy,早期卵巢癌的化疗,FIGOI，II期卵巢癌“预后好”的患者90%以上可长期无瘤存活，而且不需要辅助化疗。有高危因素的患者，30%-40%有复发的危险，25%-30%在首次手术后5年内死亡。与复发有关的高危因素：（1）包膜破裂（2）肿瘤表面生长（3）低分化（G3）（4）与周围组织粘连（5）透明细胞癌（6）腹腔冲洗液阳性（7）卵巢癌外转移,ManagementofOvarianCancer,AdvancedstagediseaseStageIII/IVPrimarycytoreductivesurgery/intervaldebulkingObtainedoptimaldebulkung(residualtumor6months)-secondarydebunkingfollowingchemotherapyPalliativetreatment(Radiotherapy,immunotherapy)unproven,Chemotherapyinovariancancer,FirstlinechemotherapyforepithelialovariancancerCHexUPandThio-Tepaprotocol(1982-1985)PACorPC(1986-1990)DDP,5-FU,Ara-c,Bleomycin,CTX.IP&IVCombination(1991-1994)Taxol,DDP/Carpa(2019-2000)Weeklytaxol/Carpa(2000-),CombinationChemotherapy,CisplatinactsbybindingtoDNAandproducingcross-linksandDNAadducts.Cisplatinisaveryeffectivedrugforovariancancer.Importantsideeffectsincludeseverenauseaandvomiting,dose-relatednephrotoxicity,ototoxicity,peripheralnerutoxicityandmyelosuppresion,CombinationChemotherapy,Themechanismofactionofcarboplatinisthesameasthatofcisplatin,thesideeffects,however,differgreatly.Themostimportantsideeffectisthrombocytopenia.Leukopeniaandanemiaalsooccurbutarelesssevere.NeurotoxicityandnephrotoxicityarelessseverewithcarboplatinthanwithcisplatinOtherimportantsideeffectincludealopeciaandmucositis.,CombinationChemotherapy,Paclitaxelactsasamitoticspindlepoison.PaclitaxelisalsoaveryeffectivedrugforovariancanceratthepresenttimeSomepatientsexhibithypersensitivitytopaclitaxel.Othersideeffectincludemyelosuppression,nerotoxicity,mucositis,diarrhea,alopcianauseaandvomiting,卵巢上皮癌的化疗,铂基础治疗方案通常联合:紫杉醇环磷酰胺阿霉素通常需要间隔3-4周至少6个周期的治疗,晚期卵巢癌的化疗,一线治疗国内顺铂+环磷酰胺(PC)顺铂+阿霉素+环磷酰胺(PAC)国外泰素顺铂泰素卡铂泰素每周疗法,CombinationChemotherapy,Combinationchemotherapymostoftenisusedaspostoperativetreatmentforadvancedepithelialovariancancer.Combinationchemotherapywithsixcoursesofcisplatinorcarboplatinpluspaclitaxelisthetreatmentofchoiceforpatientswithadvanceddisease.Coursesaregivenevery3to4weekswithmonitoringoftumorstatusbyphysicalexamination.CA125levels,andimagingstudiesifappropriate,卵巢癌病人化疗存活率,McGuireWPetal.NEnglJMed.2019,Post-TherapySurveillance,Follow-upaftertherapyinovariancancerispoorlydefined.AtthepresenttimethereisnodefinitivetestfordetectingthepresenceofmicroscopicrecurrentepithelialovariancancerForthisreasonthereremainssignificantcontroversyastowhatconstitutesoptimalposttherapysurveillance.,Post-TherapySurveillance,Screeningmodalities:1.PelvicExamination2.CA125(44%sensitivity,96%specificity,65%accuracy)3.Ultrasound(20%-89%sensitivity,75%-100%specificity)4.Second-looklaparotomy5.CTscan(44%sensitivity,86%specificity,63%accuracy)6.MIRimaging.6.Positionemissiontomography(PET)(83%sensitivity,80%specificity,82%accuracy),卵巢癌复发的诊断和治疗,首次的规范化治疗(理想的肿瘤细胞减灭术加上以足够疗程的铂类和/或紫杉醇为基础的联合化疗)70%-80%的患者可获得临床完全缓解.60%-70%的患者最终还会复发.对卵巢癌复发的诊断和治疗是卵巢癌治疗中最为棘手的问题.怎样合理处理复发性卵巢癌意见尚不统一,卵巢癌的复发类型(1),化疗敏感型卵巢癌:定义为对初期以铂类药物为基础的治疗有明确反应,且已经达到临床缓解,停用化疗6个月以上,病灶复发.,卵巢癌的复发类型(2),化疗耐药型卵巢癌:定义为患者对初期的化疗有反应,但在完成化疗相对短的时间内证实复发,一般认为,完成化疗后6个月内的复发,应考虑为铂类药物耐药,卵巢癌的复发类型(3),顽固性卵巢癌:是指在初期化疗时对化疗有反应或明显反应的患者中发现有残余病灶,例如:“二探”阳性者.,卵巢癌的复发类型(4),难治性卵巢癌:是指对化疗没有产生最小有效反应的患者,包括在初始化疗期间,肿瘤稳定或肿瘤进展者,大约发生于20%的患者.这类患者对二线化疗的有效反应率最低.,卵巢癌复发的治疗,治疗前的准备:详细复习病史包括:(1)手术分期.(2)组织学类型和分级.(3)手术的彻底性.(4)和残余瘤的大小及部位.(5)术后化疗的方案,途径,疗程,疗效.(6)停用化疗的时间.(7)出现复发的时间等.对复发性卵巢癌进行定性、分型、定位分析对患者的生活状态(PS)进行评分,对患者重要器官的功能进行评估.,目前观点认为:对于复发性卵巢癌的治疗目的一般是趋于保守性的,因此在选择复发性卵巢癌治疗方案时,对所选择方案的预期毒性作用及其对整个生活质量的影响都应该加以重点考虑.,复发性卵巢癌的手术治疗,手术对复发性卵巢癌的治疗价值尚未确定,手术的指征和时机还存在一些争论.复发性卵巢癌的手术治疗主要用于三个方面:1.解除肠梗阻2.12个月复发灶的减灭.3.切除孤立的复发灶.对晚期复发卵巢癌是先手术还是先化疗仍有争议.,ChemotherapyinOvarianCancer,SecondlinechemotherapyforepithelialovariancancerPatientswithpersistentorrecurrentdiseasesshouldbetreatedwithsecondlinechemotherapy.Unfortunately,responseratesforsecondlinechemotherapyareonly10%to30%.Regardingoftheapproach,secondlinechemotherapyforpersistentorrecurrentovariancancerisnotcurative.,SecondlinechemotherapyforepithelialovariancancerDependingontheinitialchemotherapy,secondlinechemotherapymayinclude:TopotecanPaclitaxelPlatinumIfosfamideTaxotereHexamethylmelamine,CombinationChemotherapy,对复发卵巢癌有效的新药,Survival,Early-stagediseaseFiveyearsurvivalrateforpatientswithstageIorstageIIdiseaseare80%to100,dependingonthetumorgradeAdvanceddiseaseFiveyearsurvivalrateforpatientswithstageIIIais30%to40%FiveyearsurvivalrateforpatientswithstageIIIbis20%FiveyearsurvivalrateforpatientswithstageIIIcorIVis5%RecurrentdiseaseFiveyearsurvivalrateforpatientswithnegativeSLLis50%Fiveyearsurvivalrateforpatientswithmicroscopicdiseaseis35%Fiveyearsurvivalrateforpatientswithmacroscopicdiseaseis5%,MalignantGermCellTumoroftheOvary,Twentypercentto25%ofallmalignanttumoroftheovaryareofgermcellorigin.Inthefirstdecadesoflife,70%ofovariantumorsareofgermcelloriginandonethirdaremalignantGermcelltumorsarequiterareafterthethirddecadesoflife.,1.Malignantgermcelltumoroftheovaryisverysensitivetothechemotherapy.Chemotherapyhasbeenaveryimportanttreatmentforthiskindovariantumor.2.ChemotherapyhasimprovedthesurvivalofpatientswithMalignantgermcelltumoroftheovarydramatically.Survivalratehasbeenincreasedfrom10%to90%3.Reproductivefunctioncanbepreservedforanystagepatientswithmalignantgermcelltumoroftheovary,MalignantGermCellTumoroftheOvary,Managementofmalignantgermcelltumoroftheovary,Primarytreatmentissurgical.Unilateraloophorectomywithpreservedreproductivefunctionisconsidered.PVBandPEBchemotherapyarethetreatmentofchoiceforpatientswithMGCTpostoperativelyCoursesofchemotherapyaredependingonthehighriskfactorsofthetumorandtumormakerlevels,Sexcordstromaltumors,Ovariansexcord-stromaltumoraccountforlessthan5%.Itmayoccuratanyage,althoughtheageofpeakincidenceforgranularcelltumorsisinthepostmenopausalyears.Nostandardtherapyexists.Lowermalignantpotentialandlaterecurrence,Sexcordstromaltumors,Surgeryremainscornerstoneoftreatmentforpatientswit