乳腺癌放射治疗指南之演变及解读

乳腺癌放射治疗指南之演变及解读陈佳艺交通大学医学院附属瑞金医院2016-11-2612011～2016NCCN指南变迁：保乳术后成熟部分：全乳放疗+瘤床加量可能减免术后放疗的老年患者变迁部分全乳大分割未明确部分部分乳腺短程照射包含区域淋巴结照射的大分割治疗23保乳治疗的前瞻性III期研究TrialNo.年限/FUyearsTmax切缘N+%局部复发%保乳乳房切除p米兰Ⅰ期7011973-80/202cm-25.88.82.30.01IGR1791972-80/152cm-32.4914NSNSABP-B0612191976-84/204cm-371410NSNCI2371979-87/185cm+40.52200.001EORTC9021980-86/155cm+4320120.01DBCG9051983-89/205cm-354.66.5NS#对照组除米兰Ⅰ期为根治术外均为改良根治术，研究组除米兰Ⅰ期为象限切除外均为肿块切除术4EBCTCG2005单纯保乳手术VS术后全乳放疗4:15瘤床加量对局部控制的意义作者病例数全乳剂量BOOST★局部复发率(%)随访(年)Bartelink265750Gy/25Fx/10.210266116Gy/8Fx6.2Romestaing50350Gy/20Fx/4.53.352110Gy/4Fx3.6Polgar10350Gy/25Fx/15.55.310416Gy/8Fx6.7BartelinkH,etal.JClinOncol.2007.25(22):3259-65.RomestaingPetal.JClinOncol.1997.15(3):963-8.PolgarCetal.StrahlentherOnkol.2002.178(11):615-23保乳术后全乳照射和瘤床加量6保乳术后全乳照射和瘤床加量7老年患者BCT±RTTrialInclusioncriteriaF-UYBaselinetherapyLocalcontrolRTLocalcontrolNoRTCanadian≥50Y,HR+,T1-2,cN05TAM0.6%7.7%CALGB≥70Y,HR+,T1-2,cN05TAM1%4%10.52%9%PRIMEII≥65Y,HR+,T≤3cm,PN0,gradeI-II5Anyendocrinetherapy1.3%4.1%8谁可以减免放疗？9Breastirradiationmaybeomittedinpatients≥70yofagewithestrogen-receptorpositive,clinicallynode-negative,T1tumorswhoreceiveadjuvantendocrinetherapy------CALGB的入组条件10全乳大分割基石研究：CanadianTrial每周照射次数由5次减少为3次2.66Gy×16Fvs2Gy×25F没有瘤床boost美容效果没有明显差异T1-2，N0NENGLJMED362;6:513-520,20107.5%7.4%Includingnon-invasiveRUKSTARTA研究设计2236，pT1-3apN0-1M0BCT（1055）ormastectomy50Gy/25F/5W,74941.6Gy/13F/5W,75039Gy/13F/5W,7372Gy3.2Gy3Gy3.3GyfromRMH疗程均为5周，分次剂量和总剂量逐渐减少局部控制和乳房外形分别的α/β值局部控制α/β=4.8Gy乳房外形α/β=3.1Gy2215，pT1-3apN0-1M0BCT（2038）ormastectomy50Gy/25F/5W,1105UKSTARTB研究设计40Gy/15F/3W,11002Gy2.67Gy×16FfromCanadiantrial2.67Gy×15F总剂量减少2.67Gy，疗程为3周STARTB局部控制结果14STARTB中位随访9.9年5.5%vs4.3%大分割指南推荐方案演变15全乳45-50Gy,1.8-2.0Gy/次42.5Gy,2.66Gy/次，16次全乳45-50Gy,1.8-2.0Gy/次40-42.5Gy,2.66Gy/次，15-16次Shortercourseispreferred16部分乳腺短程照射AcceleratedPartialBreastIrradiation,APBI即在低危患者中采用单纯照射肿瘤床及周围一定范围的正常乳腺组织来替代传统的全乳照射方法，从而在不影响局部控制率的前提下达到显着降低正常组织损伤并大幅缩短疗程的方法(5-6.5周下降至1周左右)SeminRadiatOncol.2005.15(2):69-7517GEC-ESTROASTRO1.Age50yr≥60yr2.Tumorsize≤3cm≤2cm3.TstagepT1–2T14.Margins≥2mm≥2mm5.GradeAnyAny6.LVSINotallowedNotallowed7.ERstatusNotallowedPositive9.MultifocalityUnifocalC.unifwithtotalsize≤2.0cm10.HistologyIDC,mucinous,tubularmedullarycolloidIDCorotherfavorable11.PureDCISNotallowedNotallowed12.EICNotallowedNotallowed13.AssoLCISAllowedAllowed14.NstageAnypN0(i-,i+)15.NodalTxpN0SLNB/ALNDSLNBorALND16.NACTNotallowedNotallowed绝经前早期乳腺癌亚临床病灶特点APBI,不同技术比较技术剂量梯度体积剂量评估处方剂量点外照射*可行靶区体积内多排插植近距离治疗*可行在插植平面内或之间水囊导管近距离治疗**~***可行水囊表面下1cm术中电子线***不可行90%等剂量曲线术中低能X线****不可行瘤床表面19保乳术后放射治疗指南稳定部分1.全乳放疗及瘤床加量始终是指南I类推荐2.单纯全乳可以接受45-50Gy的5周方案或2.66×15或16次的大分割方案3.区域淋巴结照射没有大分割的推荐4.部分乳腺短程照射没有重大更新，在RTOG0413结果之前，仍然推荐2009年出台的ASTRO“低危”标准202011～2016NCCN指南变迁：区域淋巴结照射PMRT总体结果在局部（乳房/胸壁）照射基础上单独评价区域淋巴结照射的研究在局部照射基础上单独评价内乳淋巴结照射的研究21腋淋巴结4+患者的术后放疗22EBCTCG2014TrialsofRTaftermastectomyandALNDRT:significantbenefit腋淋巴结1-3+患者的术后放疗TrialsofRTaftermastectomyandALNDRT:significantbenefit1.5B:1C4A:1C乳房/胸壁基础上区域淋巴结照射的研究FrenchTrialEORTC22922/10925MA.20入组年限1991-19971996-20042000-2007样本量133440041832主要入组标准N+或内侧/中央区N+或内侧/中央区N+或高危N0N0比例40%44.4%9.7%中位年龄575454手术类型乳房切除76.1%保乳保乳化疗%618591ER/PR-71625HR不详比例%40%16%不详乳房/胸壁剂量入组中心决定50Gy/25F50Gy/25F锁骨上淋巴结研究组和对照组45Gy/25F研究组50Gy/25F研究组45Gy/25F内乳淋巴结研究组45Gy/25F研究组50Gy/25F研究组45Gy/25F25MA20高危定义：T≥5cm，或T≥2cm，同时10枚腋窝淋巴结取样，且ER-，G3或淋巴脉管受侵入组标准比较MA.20（1832例）EORTC（4004例）入组条件LN+或高危LN-LN+或中央/内侧肿块T1-T299%95.8%N0/N110%/85%44.4%/43.1%HR阳性75%77.5%保乳手术100%76.1%区域淋巴结照射范围SC+IMN+ALNSC+IMN化疗91%54.8%NEJM:2015,373(4):317-327StudyDesign：EORTC22922/10925Phase3trialN=4004StageI-IIICentrallyormedially;orexternallywithLN(+)BCSorMastectomy+ALND/SLNDRANDOMIZENon-RNI(N=2002)•WholeBreastorchestwallirradiation:50Gy/25FxRNI(N=2002)•WholeBreastorCWirr-adiation:50Gy/25Fx•Regionalnodes:50Gy/25FxPrimaryendpointswasoverallsurvivalSecondaryendpointsincludedDFS,DistantDFSandtoxicity,BreastCancerMortalityEORTC22922/1092528EORTC22922/1092529无远处转移复发率总生存率ER–tumors:10-yearDFSinthecontrolandRNIarms：(71%and82%,P0.05);10-yearOS：74%and81%NEJM:2015,373(4):307-316StudyDesign-MA20cT4，cN2-N3wereineligibleHighriskwasdefinedasT≥5cm;T≥2cm，nodesanalyzed＜10andoneofthese:ER-,GradeIII,LVI+II(nodesanalyzed10,≥4involvednodes),Phase3trialN=1832InvasivebreastcancerLN(+)orHighrisk*LN(-)BCS+ALND/SLNDChemotherapyand/orendocrinetherapyRANDOMIZEWBI(N=916)•WholeBreast:50Gy/25Fx•TumorBedBoost(selective):10-16Gy/5-8FxWBI+RNI(N=916)•WholeBreast:50Gy/25Fx•TumorBedBoost(selective):10-16Gy/5-8Fx•RegionalnodesPrimaryendpointswasoverallsurvivalSecondaryendpointsincludedDFS,isolatedLRRFS,distantDFSandtoxicityMA2031MA2032无远处转移复发率总生存率FollowingBSC,RTshouldinclude,IfpN+Breastonly5BreastandregionalnodesbutnotIMN50BreastandregionalnodesincludingIMN30*Abstain16PMRTshouldinclude:Chestwallonly11.4ChestwallandregionalnodesbutnotIMN40.9ChestwallandregionalnodesincludingIMN15.9*Abstain31.82015St.GallenConsensusHighriskfactorsofIMNmetastasis1,679ChinesepatientswereunderwentERM:1956-2003Highriskfactorsincluding:(1)patientswith4ormorepositiveAL