血液生物标志物(CTC ctDNA)在非小细胞肺癌治疗中的作用-1

血液生物标志物(CTC&ctDNA)在非疗压力而不停演变中ogyspecimanogyspecimanlogyspecimanCTCALKROS,c-ticmonitoringanddiagnosis••••A••••EffusionPleuraleffusionAscites••Lymphnode•Bonemarrow?AEExsome外泌囊泡⼩体forliquidbiopsy对血管的内渗作用(上皮向间叶细胞落DanielA.Haber,etalCANCERDISCOVERYJUNE2014CTC检测方法=CTC富集技术ü免疫磁珠(负向富集+CTC检测技术ü靶向PCRü普通PCRploRareCellSearch®CyttelTMCanpatrolTMCTC-BiopsyⓇ珠负向富集PCR技术富集技术荧光免疫磁珠负向富集、Fish技术ISET(滤膜)杂交RNA分析ISET(滤膜)记异性肺癌早期(I期)0%20%(2/10)未报道未报道中晚期敏感性否25%(22/87)61%-88%30%40%h1样本h1样本是是是是人150例其他肿瘤(150例)肝癌30例结直肠癌30例乳腺癌30例胃癌30例食管癌30例560例50例C(21例D)79例D100例A50例人150例其他肿瘤(150例)肝癌30例结直肠癌30例乳腺癌30例胃癌30例食管癌30例560例50例C(21例D)79例D100例A50例D150例A肺癌560例A肺部良性疾病350例A健康人150例A肺癌100例D肺部良性疾病50例D健康人50例D其他肿瘤150例A350例非小细胞肺癌100例B50例C临床试验设计(1210例,最大样本量)B：术前术后CTC监测1210例受试者B：术前术后CTC监测1210例受试者D：基线CTC、CEA、CYFRA21-1、SCCD：基线CTC、CEA、CYFRA21-1、SCC、NSE检测331例A100例B300例A50例DJiataoLou,etal.PlosOne2013;YueYu,etal.TranslOncol2012;XiaoxiaChen,etal.JTO2015辅助诊断：CTC对肺癌的诊断显著癌诊断的准确性(AUC值)AUC值P值CTC0.91P<0.0001CEA0.56NSE0.61CYFRA21-10.71SCCA0.49LouJT,WangL,etalInsubmission肿瘤大小CT特异性(％)CT＋CTC特异性(％)20-30mm(n＝44)CNSCLCNSCLC,1st-linecarboplatin,paclitaxel(d);NSCLC,2nd-linepemetrexed(e)BaselineCTscanswerebeforetherapyinitiationandCTCmeasurementsbeganatorshortlyafterthefirsttreatment.上海市肺科医院数据：CTC可用于评估化疗疗效，特别是针对SD患者和治疗后缓慢进展的患者•CTC可评估肿瘤功能状态，弥补RECIST方法不足AACRAACRCTC群RClinCancerResNovember15CirculatingTumorDNA(循环肿瘤DNA)的DNA片段释放入血(CfDNA)；cfDNA片段长度通常是160-180bp；来源于肿瘤细胞的DNA片段是ctDNA；ctDNA的绝对含量，随肿瘤负荷(tumorburden)和治疗反应而发生变化Crowley,E.etal.Nat.Rev.Clin.Oncol.10,472–484(2013)iTranslMedFebraFrequencyofcaseswithdetectableFrequencyofcaseswithdetectablectDNA(%)ctDNA水平–癌症进展分期ctDNActDNA水平–肿瘤类型1100806040200•脑部肿瘤由于血脑屏障不易检测到ctDNAARMsandCobasMethods：McLartyetalMOJCellScienceReport015一致性为58%agnosedlocallycedstageIIIABtastaticchemotherapynaveNSCLCnotsuitableforcurativetreatmentaorundtimewithinweekstionsstingpy•PDr.ReckGermanyarySP:97%PPV:NPV:•Sensitivetestingmethods(≥10%tumorcellcontent)testedtestedolocalctDNAcirculatingfreetumorderivedDNAWHOWorldHealthOrganization1.Recketal.2015;2.Lindeman2013者者8血浆与组织一致性T790MTMT790M阳性人群中，有••不同状态人群对RocileLnib的ORR•StageIV•StageIV•PS0-2；•cf-DNAEGFRmutationbyddPCR；•Tumorsampleavailable；CTONG1405(BENEFITStudy)ASingle-arm,Open,MulticenterStudyEvaluatingEfficacyandSafetyofFirst-lineGefitinibTreatmentinMetastaticLungAdenocarcinomaPatientswithSensitizingEGFRMutationDeterminedbyddPCRinPlasmacell-freeDNAgegefiQnib250mg/dTheprimaryendpoint:objectiveresponserate(ORR;RECIST1.1).Secondaryendpoints:diseasecontrolrate,progression-freesurvival,overallsurvival,safetyevaluationMsensitizingdeletioninexon19;inemutationL858R.CAncerPersonalizedProfilingbydeepSequencingAM.Newman,etal.NatMed20VolumeVolumeIssues14January2016,PagesCTC/ctDNA互补将提高T790m的检出率CTC/ctDNA/组织标本的不一致性，可能由技术造成，也可能与不同的肿瘤细胞群TilakK.Sundaresan，ClinCancerRes;2015CTC的临床应