头颈肿瘤治疗易俊林forjournalclub.ppt

头颈部肿瘤治疗,头颈肿瘤的治疗手段,手术治疗放射治疗化学治疗以上三者的综合治疗生物反应调节剂分子靶向治疗中医中药,手术治疗,主要手段之一，超过100年历史手术治疗与放射治疗的综合成为许多病种的标准治疗模式,手术治疗缺点,1根治性手术通常导致外形改变2影响重要器官的功能，如语言、吞咽、咀嚼等3晚期疾病局部和远地失败率很高,头颈部肿瘤功能保全性治疗,目的,保留喉的功能气道：无永久性的气管套管语言功能：发音清晰，可以自由交谈保留进食功能：不用鼻饲保留舌的功能：语言、吞咽、咀嚼,治疗对象,局部晚期喉癌、下咽癌和口咽癌（III或IV期）舌根癌可手术切除患者有保留喉正常功能的愿望,治疗模式,单纯放射治疗术前放疗化疗+放疗综合治疗诱导化疗+放射治疗同步放化疗放疗+辅助化疗,Radiotherapy,适应症,局部晚期头颈部鳞状细胞癌（III或IV期）可手术切除或无法手术切除,治疗方法,常规分割放射治疗每日1次，2Gy/次，5次/周超分割放射治疗每日2次，1.2-1.5Gy/次,5次/周加速超分割放射治疗每日3次，1.5Gy/次,5次/周,常规分割的单纯放疗,作者例数部位结果器官保存,Harwood293glottic5y-OST2N080%T3N069%T4N063%61%N+43%,Harwood410supra-5y-RFT1-2N070%T1-2N060%(1983)T3-4N054%T3-4N064%N+39%,金晶238glotticT1N05y-OS84%91.6%,舌根癌治疗,作者病例数治疗疗效功能保存Barrett20ER+B5yrLC86%86%2002US5yrOS30%Lusinchi108ER+B5yrLC64.2%64%1989France5yrOS26%Harrison67ER+B5yrLC89%89%1998USSpiro120SLC30%1974USKrausS18%rateoffirstfailure1996USNisi79S+R5yrLC82%1998USThawley101R+S5yrLC74%1983US,超分割放疗的随机分组研究,方法5-yLC,EORTCHFX52%(1992)StandardRT(70Gy)18%,RTOG9003StandardRTbetterLCfor(2000)HFXHFXandboostRTAFXwithsplitcourse(p=0.045,0.050)AFXConcomitantBoostRt,P=0.001,RTOG90-03,fractionationschedules,Conventional,Acceleratedwithsplit,Hyperfractionated,70Gy-35fx-7wks,67.2Gy-42fx-6weeks(including2-weeksplit),72Gy-42fx-6wks,81.6Gy-68fx-7wks,AcceleratedwithConcomitantboost,Fu2000,RTOG90-03,loco-regionalcontrol,Fu2000,RTOG90-03,survival,Fu2000,PreoperativeRT,RTOG73-03,Purpose:Whichoneisprefer?PreoperativeRTorPostoperativeRT?MaterialsHypopharynxcarcinomaResourse:FranceGustaveRoussyCancerInstituteResults:4yrOS38%inpostoperativeRT33%inpreop-RTConclusion:PrefertopostoperativeRTCancer197739:1445-1449,Preversuspost-operativeradiotherapyofresectablesquamouscellcarcinomaoftheheadandneck.11reportspublishedduring1965-91，evaluatingpre-vs.post-operativeRTgivenatcomparabledoselevels.2reportswereofprospective,randomisedandnineofretrospectivecomparisons.WennerbergActaOtolaryngol1995，115(4):465-74,Theelevenstudiescomprised1,358patients(326inprospectivestudies).Thebulkoftheevidenceclearlysuggestspost-operativeloco-regionalcontroltobesuperiortopre-operativeRT.However,thisseemstobeoffsetbythesubsequentdevelopmentofdistantmetastasesormetachronoustumours.WennerbergActaOtolaryngol1995，115(4):465-74,Chemotherapy,理想的放疗增敏剂,选择性作用于肿瘤，而非正常组织肿瘤内适宜的药物浓度使肿瘤放射剂量更为有效增加放射损伤抑制放射损伤修复增加细胞毒性途径（Apoptosis)改变细胞周期分布至放射敏感期非细胞毒性，如有则仅表达抗肿瘤效果最佳给药途径和时间,化疗增敏的理论基础,优点控制潜在或亚临床转移灶化疗药物起放射增敏作用提高局部控制率改善远期生存率缺点正常组织毒性限制了放化疗同时应用,放疗合并化疗常用的药物,核苷酸类似物:5-FU拓扑异构酶I抑制剂:喜树碱类泰素铂类:顺铂,化疗与放射治疗的结合方式,诱导化疗同步放化疗辅助化疗,诱导化疗+放疗,治疗模式,诱导化疗1-3周期（CF方案）,PR+CR,NR,根治性放疗,手术+术后放疗,CF:DDP100mg/m2d1,5FU1000mg/m2d1-5RT:66-70Gy,诱导化疗+放射治疗的II期研究,1991PfisterOro-,hypo-DDPbased43%(CR)-69%(n=40)larynealcax3cycles84%(OP)1994SusanOro-,Hypo-DDPbased37.5%(CR)2-OS58%85%(n=42)Larynealcax3cycles65.0%(OP)2-FFS42%1995PfisterOro-DDPbased42%(CR)5-OS41%94%(n=33)x3cycles64%(OP)5-FFS42,RT,RT,RT,作者,病种,治疗,反应率,疗效,保喉率,诱导化疗的III期随机分组研究,例数部位分期化疗分组结果保喉率,VA332喉癌III,IV2-3CF放疗2y-OS68%66%(1991)(98%CR/PR)手术+放疗68%,GETTEC68喉癌T32-3CF放疗2y-OS69%20%(1998)(42%CR/PR)手术+放疗84%,EORTC202下咽/喉II-IV2-3CF放疗3y-OS57%42%(1996)(原发灶54%CR)手术+放疗43%,Italy237下咽鼻旁窦III-IV4CF局部治疗3y-OS37%(1994)口腔口咽(不能手术者44%CR)诱导化疗+局部治疗3yOS33%,结论(1),诱导化疗+放疗并未提高生存率，治疗结果与手术+术后放疗相似，但化放疗可以明显降低远处转移率局部复发多发生于化放疗组。2/3患者可通过化放疗保留喉的正常功能。,VAlaryngealcancerstudyNEJM1991324(24)1685-90,诱导化疗加放疗无严重的副作用。临床或病理CR，无病生存率显著高于未达到CR者。,VAlaryngealcancerstudyJCO1994;12(8):1592-99,结论(2),诱导化疗组的缺点,病例选择部分患者行单纯放疗即可治愈。部分患者不必行全喉切除。无单纯放疗组做对照，无法显示化疗的优势。,术后化疗+放疗或同步化放疗,预后不良的病理特点：1多个淋巴结阳性2淋巴结包膜外受侵3切缘近或阳性4切缘原位癌,术后序贯化疗研究,RTOG81-16,非随机试验比较化疗+手术+放疗（1）VS手术+化疗+放疗（2）1yrOSand2yrOS后者比前者稍好。5yrOS:27%in(1)and23%in(2)由于首先接受化疗的病人中，20-25%拒绝手术随后的随机试验选择（2）作为实验组,RTOG83-22andIG0034,可手术头颈鳞癌,手术,分层,部位口腔、口咽、下咽、喉,分期切缘,随机分组,化疗+放疗,放疗,化疗方案：DDP100mg/m2d15FU1g/m2/24hd1-5Q3wx3cycle放疗方案：低危组50Gy高危组60Gy,n=222,n=224,结果,LC4yrOS4yrDFSDMS+C+R74%46%46%15%S+R71%44%38%23%PNSNSNS0.03,结论,手术后序贯化放疗与单纯放疗比较，未能提高局部控制率、总生存率和无瘤生存率手术后增加化疗降低远地转移率,术后同步放化疗法国III期随机分组试验,可手术III期或IV期口腔、口咽、下咽、喉、原发不明颈转移癌,手术（原发灶和颈清扫）,颈淋巴结病理特点ECE?,无出组,是，随机分组,单纯放疗n=44,同步放化疗n=39DDP50mgweekly,结果,LFOSDFSLF-freeOSDMfreeOSSS+R43%S+CHR21%P0.08.01.02.05NS,2yr46%5yr13%,2yr72%5yr36%,2yr59%5yr55%,2yr84%5yr70%,2yr44%5yr23%,2yr68%5yr45%,2yr81%5yr49%,2yr73%5yr58%,LF:localfailure,IntJRadiatOncolBiolPhys1996,结论,术后同步放化疗提高局部控制率和生存率不增加放射并发症,Concurrentchemoradiotherapy,头颈部肿瘤同步放化疗随机研究结果,StudyPtGroupExperimentalArmOutcomeMerlanoUnresectableCF24%v10%(p=0.01)(1996)Brizel“Advanced”HFRT+CF3yr:LC70v44%(1998)N=56CFx2OS55v34%(p=.07)WendtUnresectableRT+PFL3yrSurvivalimproved(1998)N=13048v24%(p0.0003)CalaisUnresectableRT/DDP3yrSurvivalimproved(1999)OPXN=109+5FU51v31%(p=0.02)AdelsteinunresectableDDP/5FU3yros37%VS23%P=.014(2003)2953yrDFS51%v33%P=.01Budach“advanced”HFRT+2yrSurvivalimproved(2001)OPX,HPXN=3845FU/MMC49v39%(p=0.05),FinalResultsofthe94-01FrenchHeadandNeckOncologyandRadiotherapyGroupRandomizedTrialComparingRadiotherapyAloneWithConcomitantRadiochemotherapyinAdvanced-StageOropharynxcarcinoma,DenisFJCO2004,Materialsandmethods,Results,Treatment5yr-OS5yr-SDFS5yr-LRArmA16%15%25%ArmB22%27%48%P0.050.010.002,Results,Prognosticfactors,StageIVHemoglobin125g/LStandardtreatment,Conclusion,ConcomitantradiochemotherapyimprovedOSandLRDoesnotstatisticallyincreaseseverelatemorbidity.Anemiawasthemostimportantprognosticfactorforsurvivalinbotharms.,PignonJPLancet2000,Meta-AnalysisofChemotherapyonH349:2091-8.,Purpose,Optimzingthetimingofchemotherapycombinedwithradiotherapyfororganpreservationinpatientswithlocallyadvancedheadandneckcarcinoma,RTOG91-11,顺铂/5FUx2n=173同步放化疗（顺铂）n=172单纯放射治疗n-173,顺铂/5-FURTx1全喉切除RT,CR,PR,NRor1cm无远地转移,NEnglJMed2003;349:2091-8,Laryngealpreservation,NEnglJMed2003;349:2091-8,ConcurrentvsinductionP=0.005ConcurrentvsRTaloneP=0.001InductionvsRTaloneP=0.27,Local-regionalcontrol,ConcurrentvsinductionP=0.003ConcurrentvsRTaloneP65Gy).3.fewerthan20%ofpatientscouldhavenasopharynxcancer,Results,Totally20comparisonswasfound,3,192casesOR95%CIPvalueconcomitantCTplusRTvsRT0.620.52-0.740.00001RTissameinbotharm0.620.52-0.750.73),Weberetal,2003,RTOG91-11,挽救性全喉切除术后并发症,Weberetal,2003,结论,保守治疗失败后，挽救性手术后局部控制率好。术后生存率在三组中无差别术后并发症较高，尤其是咽瘘（30%）。,Weberetal,2003,RTOG91-11,颈部淋巴结的处理,非随机研究,AnnArbor58例N2和N3，CR者行颈清扫结果与CR而观察的病人无差别。Italian,CR252yrLC85%CR182yrLC17%,N3病人颈部无2年DFS,MSKCC68例舌根癌外照射+近距离在近距离治疗时行颈清扫LC100%,70%标本无癌,Australian52例N2-3，,28例pCR6复发,24例CR19例死亡,结果,N1-2病人，淋巴结对非手术治疗的反应可以指导处理，CR者观察，CR者颈清扫N3病人，行计划性颈清扫,随机研究,PhaseIIIclinicaltrailinresectablestageIIIandIVheadandneckcancerLavertuPetal.Head&neck1997,材料和方法,合格病人随机分组,RTalone50-55Gy,Concurrentchemo+RT,无效或进展,3-6周后手术,所有疗前N2-3病人治疗结束后颈清扫,NON-CR残存部位手术,5-Fu1g/m2/dd1-4continuousDDP20mg/m2/d1-4inWeek1and4,CRorPR,继续放疗到65-72Gy,4-6周评价,CR观察,CRPRNDP局部效果放疗50331025同步5045410区域效果放疗N1106220N2-327131013同步N188000N2-32617711,结果,结果,6CR,0,6,dissection,41no,38CR3CR,N0-1n=47,43progress,5CR1CR,Patholog,recurrence,14CR4+9CR8+,0,35,18no,12CR6CR,N2-3n=53,36progress,18CR17CR,3,未来