软组织肿瘤精PPT课件.pptx

成人软组织肉瘤化疗,Contents,OverviewDrugsTreatmentneoadjuvantchemotherapyadjuvantchemotherapyAdvancedormetastaticdiseaseschmeotherapytargetedtherapy,Contents,OverviewDrugsTreatmentneoadjuvantchemotherapyadjuvantchemotherapytargetedtherapy,Sarcomasconstituteaheterogeneousgroupofraresolidtumorsofmesenchymalcelloriginwithdistinctclinicalandpathologicalfeatures,成人软组织肉瘤（Softtissuesarcomas，STSs），包括一组发病相对较少，组织学多样的恶性肿瘤。起源中胚层和外胚层。占成人恶性肿瘤的1%和儿童恶性肿瘤的5%。尚无特别有效的治疗方法，需多学科联合。,Categories,Sarcomasofsofttissues(includingfat,muscle,nerveandnervesheath,bloodvessels,andotherconnectivetissues)Sarcomasofbone.,Theanatomicsiteoftheprimarydisease,Extremities(60%)thetrunk(19%)retroperitoneum(15%)headandneck(9%),Riskfactors,Age.Softtissuesarcomascanoccuratanyage,butoverallaremorecommoninolderadults.Theaverageageatdiagnosisis57years.Certaintypesofsarcomasaremorecommoninchildren,however.Chemicalexposure.Beingexposedtocertainchemicals,suchasvinylchlorideanddioxin,canincreasetheriskofsofttissuesarcomas.Radiationexposure.Previousradiationtreatmentforothercancerscanincreasetheriskofsofttissuesarcomas.,Signsandsymptoms,anewlumporalumpthatisgrowinganywhereinthebodymayormaynotcausepainmayincludeabdominalswellingoralumpintheabdomennauseavomitingheartburnabdominalpainbloodinvomitorstool,Adultsofttissuesarcomadiagnosed,Incisionalbiopsy:Theremovalofpartofalumporasampleoftissue.Corebiopsy:Theremovaloftissueusingawideneedle.Excisionalbiopsy:Theremovalofanentirelumporareaoftissuethatdoesntlooknormal.,coreneedlebiopsy,Pathologyandstaging,thetypeofsofttissuesarcomathestageofthecancer(howfarthecancerhasprogressed)thegradeofthetumour(howabnormalthecancercellslookandbehave),Pleomorphicsarcomaalsoknownasmalignantfibroushistiocytoma(MFH)GISTsLiposarcomaleiomyosarcomasynovialsarcomamalignantperipheralnervesheathtumors,IncidenceofSoftTissueSarcomaSubtypes(1978-2001),SitesofMetastasis,GaddM,etal,AnnSurg,1993,Contents,OverviewDrugsTreatmentneoadjuvantchemotherapyadjuvantchemotherapytargetedtherapy,Chemotherapy,SingleAgentsDoxorubicinIfosfamideDacarbazineGemcitabinePaclitaxelDocetaxel,Chemotherapy,PemetrexedTemozlomideIrinotecanTopotecanPelyatedliposmaldoxorubicinTrabectedin,Doxorubicin,Thesingleagentresponserates(RR)areintherangeof20to30%survivalintherangeof7.7-12monthsThebestresponseratesareseenwithdosagesintherangeof75mg/m2to90mg/m2,Doxorubicin,Epirubicinisalesscardiotoxicanalogofdoxorubicin,whichfailedtodemonstrateanybenefitascomparedtodoxorubicinliposomaldoxorubicincanbeusedinpatientswheredoxorubiciniscontraindicated,buttheresponseratesofthisdrugasasingleagentarelowerthantheconventionaldoxorubicin.,Ifosfamide,adose-responserelationshipandhigherdosescanbeusedasitlackscardiotoxicitymonotherapywithanidenticaldose(9g/m2),givenoverthreedays,byeithercontinuousinfusionorthree-hourinfusionsdaily,Dacarbazine,incombinationwithdoxorubicinandifosfamide(MAID)givenasashortinfusionof1.2g/m2over20minuteswiththeavailabilityofeffectiveantiemetics.,Temozolamide,Temozolamide,theoralequivalentofdacarbazine,appearstohavethesameactivityagainstleiomyosarcomaaswell.,Trabectedin(Ecteinascidin-743,ET743,Yondelis),Thistetrahydroisoquinsolinemoleculewasderivedoriginallyfromatunicate,orseasquirt,Ecteinascidiaturbinate(foundintheCarribbeanandMediterraneanwaters)Apooledanalysisof183patientsfromthethreesinglearmphaseIIstudies1.5mg/m2administeredasa24-hourinfusiononceeverythreeweeksInthisanalysisthoughtheORRwasonly7.7%,therateoftumorcontrol(i.e.,ORRplusminorresponsesplusdiseasestabilization)was51%.,Contents,OverviewDrugsTreatmentneoadjuvantchemotherapyadjuvantchemotherapyAdvancedormetastaticdiseaseschmeotherapytargetedtherapy,Treatment,surgerySurgeryisthemostcommontreatmentformanysofttissuesarcomas.Dependingonthesizeandlocationofthesarcoma,allorpartofthetumourmayberemoved.Ifthewholetumourisremoved,awidemarginofhealthytissuearounditisalsoremoved.Inmanycases,limb-sparingsurgerycanbedoneforasofttissuesarcomathatoccursinanarmorlegandamputationcanbeavoided.However,insomecases,softtissuesarcomainalimbmayrequirethelimbtobeamputated.radiationtherapyRadiationtherapymaybeusedbeforeoraftersurgeryor,lesscommonly,insteadofsurgery.chemotherapyIfthesofttissuesarcomahasspreadtootherpartsofthebody,chemotherapymaybeusedtocontrolthecancerandrelievesymptoms.Chemotherapyissometimesusedbeforesurgerytoshrinkatumouroraftersurgerytohelpreducethechanceofthecancerrecurring.,软组织肉瘤:传统治疗,局限期肉瘤:扩大范围的手术为标准治疗对于高度或中度复发风险或者切缘阳性的软组织肉瘤而言，通常需行术后放疗1三维适形放疗,近距离放疗,或调强放疗,1.ClarkMA,etal.NEnglJMed.2005;353:701-711.2.WunderJS,etal.LancetOncol.2007;8:513-524.,但是仍有50%的软组织肉瘤患者会出现远处转移2,SurgicalManagement,MainstayoftreatmentforallSTSoftheextremityiswidelocalexcision(+/-)XRTAdjuvant/neoadjuvantRoleofneoadjuvantchemotherapyWidenblocresection1-2cmmarginsinalldirectionsLimitingfactors:neurovascularjuxtapositionBonyjuxtaposition,RadicalSurgicalMargin,Amputation,新辅助化疗,134例患者，单纯手术组与新辅助化疗+手术，每组67例。成人高危STSs（肿瘤or=8cm，不论分级如何；或分级为II/III，但肿瘤5cm，以及深部肿瘤,RoleofAdjuvantChemotherapy,Sarcomameta-analysiscollaboration,lancet,19971568patientsfrom14studiesMedianfollow-up9.4years10-yr.DFSimprovedfrom45to55%(p=0.0001)Local10-yr.DFSimprovedfrom75to81%(p=0.016)OSonlyimprovedfrom50to54%(p=0.12)Datadoesnotsupportroutineuseofadjuvantchemotherapyoutsideaclinicaltrial,AdjuvantChemotherapyTrials,Meta-Analysis#2,Metastaticdiseaseschemotherapy,AnEORTCSTBSGstudy,Atotalof2,185patientswithadvancedsofttissuesarcomaswhohadbeentreatedinsevenclinicaltrials,Results,Results,MetastaicSoft-TissueSarcomaschemotherapy,MetastaicSoft-TissueSarcomaschemotherapy,Dose-intensivechemotherapywithgrowthfactororautologousbonemarroworstem-celltransplantsupportinfirst-linetreatmentofadvancedormetastaticadultsofttissuesarcoma:aclinicalpracticeguideline,Dose-intensivechemotherapywithgrowthfactorsupportisnotrecommendedinthefirst-linetreatmentofpatientswithinoperablelocallyadvancedormetastaticsofttissuesarcoma.Thedataareinsufficienttosupporttheuseofhigh-dosechemotherapywithautologousbonemarroworstem-celltransplantationasfirst-linetreatmentinthisgroupofpatients.Eligiblepatientsshouldbeencouragedtoenterclinicaltrialsassessingnovelapproachesorcompounds.,CombinationRegimensbeyondIfosfamideandAdriamycin,Fixed-doserategemcitabineplusdocetaxelasfirst-linetherapyformetastaticuterineleiomyosarcoma:aGynecologicOncologyGroupphaseIItrial,Forty-twowomenenrolled,with39evaluableforresponse900mg/m2over90minutes,d1andd8;docetaxel100mg/m2onday8,Withgranulocytegrowthfactorsupportdaynineofa21-daycycle.,Response,ORR15of42patients(35.8%overall;CR4.8%,PR31%,90%CI23.5to49.6%),11(26.2%)SDmedianprogression-freesurvival(PFS)4.4months(range0.4to37.2+months)Medianoverallsurvival16+months(range:0.441.3months),Fixed-doserategemcitabineplusdocetaxelassecond-linetherapyformetastaticuterineleiomyosarcoma:aGynecologicOncologyGroupphaseIIstudy,Forty-onewomenenrolled,with48evaluableforresponseunresectableuterineleiomyosarcomaprogressingafterpriorcytotoxictherapygemcitabine900mg/m2,d1andd890minutes,docetaxel100mg/m2d8,21-daycyclewithgranulocytegrowthfactor,CR6.3%(3/48),PR20.8%(10/48)ORR27%(95%confidenceinterval15.3%41.8%).Anadditional50%(24/48)SD,clinicalbenefitrateof77%.MedianPFSforall48patientswas6.7+months(range0.727+months),Adverseevents,Thepredominanttoxicitywasmyelosuppressionleukopeniagrade3(14.5%),grade4(8.3%)thrombocytopeniagrade3(29%),grade4(10.4%)neutropeniagrade3(12.5%),grade4(8.3%)anemiagrade3(20.8%),grade4(4.2%).,RandomizedPhaseIIStudyofGemcitabineandDocetaxelComparedWithGemcitabineAloneinPatientsWithMetastaticSoftTissueSarcomas:ResultsofSarcomaAllianceforResearchThroughCollaborationStudy002,Fixeddoserate10mg/m2/10mininfusingemcitabineat1200mg/m2d1andd8ingemcitabinearmGem-Docarm,gemcitabnedose900mg/m2fixeddoserateinfusion90min,d1andd8;docetaxel100mg/m2d160minRepeatevery21days,InvestigationalNewDrugs(targetedtherapy),Mammaliantargetofrapamycin(mTOR)inhibitorsmTORinhibitorsinclinicaldevelopmentThreerapamycinanalogs:CCI-779(temsirolimus),RAD001(everolimus),andAP23573(deforolimus)Insulinlikegrowthfactor1receptor(IGF-IR)inhibitorsOthers,AngiogenesisandSTSs,AngiogenesisplaysanimportantroleinthegrowthanddisseminationofSTSstheVEGF/VEGFRpathwayplaysthemostimportantroleHighVEGFexpressionisanindependentpoorprognosticfactorforincreasedriskofmetastasesanddecreasedoverallsurvival,Compassionateuseofbevacizumab(Avastin)inchildrenandyoungadultswithrefractoryorrecurrentsolidtumors,Bevacizumabwasadministeredat510mg/kgbodyweightintravenouslyevery23weeks,Mostpatientsreceivedchemotherapyinadditiontobevacizumab,Others,苹果酸舒尼替尼索坦：药物结构,小分子吲哚酮类化合物分子式：C22H27FN4O2C4H6O5分子量：532.6ATP位点竞争性抑制剂抑制磷酸化和激活阻断信号传导,SutentProductMonograph,舒尼替尼主要作用靶点,*对于GIST而言尤其重要；*对于GIST/乳腺癌和小细胞肺癌而言尤其重要,舒尼替尼同时具有抗肿瘤血管生成与抗肿瘤细胞增殖双重效应,SandrineF,etal.Nature,2007,舒尼替尼治疗腺泡软组织肉瘤,S.Stacchiotti,etal.AnnalofOncology,2011Feb,舒尼替尼治疗非GIST软组织肉瘤,晚期/转移性非GIST软组织肉瘤,既往可接受1-2个化疗方案失败，ECOGPS0-2(N=53),持续治疗直至疾病进展,舒尼替尼37.5mg,每天持续口服,II期临床：多中心、前瞻性舒尼替尼持续37.5mg口服ArmA:血管结缔组织肿瘤(n=18)平