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结直肠癌新辅助治疗直肠癌术前放化疗2021/1/122新辅助治疗的目的◼提高手术切除率◼提高保肛率◼降低局部复发◼延长患者无病生存期2021/1/123推荐◼T3和/或N+的可切除直肠癌患者，推荐术前新辅

助放化疗。◼直肠癌术前化疗推荐以氟尿嘧啶类药物为基础的化疗方案2021/1/1242021/1/1252021/1/1262021/1/1272021/1/1282021/1/1292021/1/12102021/1/12112021/1/121220

21/1/12132021/1/1214结肠癌肝转移术前化疗2021/1/1215推荐◼结直肠癌患者合并肝转移，可切除或者潜在可切除，推荐术前化疗或化疗联合靶向药物治疗：西妥昔单抗（推荐用于K-ras基因状态野生型患者），或联合贝伐珠单抗◼化疗方案推荐FOLFOX，或者

FOLFIRI，或者CapeOx，2021/1/1216livermetastasesNotresectableresectablechemotherapy85%15%+otherlocationsofmetastaseschemotherapy50%50%Patientswit

hmetastaticcolorectalcancer5ySurvival:5%5ysurvival:5%Metastaticcolorectalcancer5ysurvival:20-40%2021/1/1217Responserate,9,8,7,6,5,4,3,6,5,4,3,2,10,

0ResectionrateofmetastasesandtumorresponseStudiesincl.selectedpats.(livermetastasesonly,noextrahepat.d

isease)r=.96,p=.002Studiesincl.allpatientswithmetastaticCRC(solidline)r=.74,p<.001PhaseIIIstudiesinmeta

staticCRC(dashedline)r=.67,p=.024,p=.024Folprecht…Köhneetal,AnnOncol20052021/1/1218新辅助化疗优势◼患者体内化疗药物的药敏试验◼清除微小转移灶◼观察甄别出快速进展病例◼提高R0切除

率？并减少切除的正常肝组织◼延长生存期？2021/1/1219Adjuvant,neoadjuvant,conversiontherapyforCRClivermetastases•Resectable-adjuvant-neo-adjuvant•Unresectable-Conversion

chemotherapy2021/1/1220ColorectalCaR0ResectionofMetastasesControversy:AdjuvantTherapy?USAYes(KemenyNEJM1

999)EuropaNo(LorenzNEJM2000)2021/1/1221KemenyetalNEJM1999and2005Livermetastases:adjuvantHAI+i.v.CTXp=0.02Media

noverallsurvivalFong0-2Fong3-5HAI+systemic83.3mo60.0mo(10y:38.7%)systemic82.8mo38.3mo(10y:16.3%)p=0.132021/1/1222LV5

FUvs.FOLFIRIasadjuvanttherapyfollowingresectionofCLM-DFS0.000.250.500.751.00153114704122LV5FUs+IRI15395654425

LV5FUsNumberatrisk012243648MonthsLV5FUsLV5FUs+IRIadjustedLogrankp=0.43HR=0.89:95%CI[0.66-1.19]Treatment1-yearDFS:63%vs.7

7%2-yearDFS:46%vs.51%Ychouetal.ASCO20082021/1/1223AdjuvantChemotherapyforCRClivermetastases➢YES！➢Whichpatients

?高复发风险➢whichregimen?化疗？HAI？➢方案？FU、OXA？Target？2021/1/1224EORTCphaseIIIstudy40983研究设计RandomizeSurgeryFOLFOX4FOLFOX4Surgery6c

ycles(3months)6cycles(3months)❖364例潜在可切除肝转移(metachronousorsynchronous)，4个以上病灶，无肝外转移2021/1/1225EORTCStudy40983mobidityHepaticfailureBiliaryfistula

bleedingmotalitychemo24.5%6.4%5.5%2.7%0.9%surgery13.3%1.6%1.6%2.3%1.6%CTSP3-yFPS%42.433.20.025手术情况Peri-opCT(N=182)Surgery(N=182

)Operated159(87.4)170(93.4)Resected151(83.0)152(83.5)Notresected8(4.3)18(9.9)2021/1/1226乐沙定，伊立替康和持续滴注5-FULV(FOL

FOXIRI)两周方案和Folfiri相比一线治疗转移性结直肠癌：III期临床结果（GONO）A.Falcone,etalASCOGI2006,#227不能切除的结直肠癌肝转移新辅助化疗2021/1/1227伊立替康，乐沙定和持续滴注5-FULV(FOLFOXIRI)两周方案和Folfi

ri相比一线治疗转移性结直肠癌：III期临床结果（GONO）*DouillardLancet2000**MasiAnnOncol2004临床设计FOLFIRI*RCPT-11180mg/m21-hd.1L-LV100mg/m22-hd.1

,25FU400mg/m2bolusd.1,25FU600mg/m222-hd.1,2q.2wksx12个周期FOLFOXIRI**CPT-11165mg/m21-hd.1LOHP85mg/m22-hd.1L-LV200mg/m22-hd

.15FU3200mg/m248-hCId.1q.2wksx12个周期分层⚫中心⚫PS0/1-2⚫辅助化疗FOLFIRI方案进展后，推荐含乐沙定的方案2021/1/1228A.Falcone,ASCOGI2006,#227外部评

估FOLFIRI(122pts)FOLFOXIRI(122pts)完全缓解6%7%部分缓解28%53%完全+部分95%可信区间34%0.25-0.4360%*0.51-0.68稳定34%21%进展24%11%不可评估8%8%*p<0.001有效率(ITT分

析)化疗后手术切除率(所有病人)FOLFIRI(122pts)FOLFOXIRI(122pts)RO6%(7pts)15%*(18pts)R11%2%Explorative8%1%*p<0.033疗效结果主要目标：RR次要目标：PFS,OS,postsur

gicalresectionsn,safetyQOL2021/1/1229RescueSurgeryforUnresectableColorectalLiverMetastasesDownstagedbyChemotherapyAMode

ltoPredictLong-termSurvival◼Retrospectivestudy◼1104caseswithunresectablelivermetastases◼Chemotherapyregimens：5-FU/LV/OXAorIRIorboth◼

138(12.5%)achievedsecondarycurativehepaticresection◼Survivalrate:5-year33%10-year23%AdamRetal,Annsurg.2004;240:644-6572021/1/1230Resectionoflivermet

astases:non-selectedpatientstreatedwithtargeted/cytotoxicagentsFirstauthorNRegimenRRResectionrateFolprecht21Cetuximab/irinotecan67%19%/AIO(24%)*

DiazRubio43Cetuximab/FOLFOX479%19%Rougier42Cetuximab/FOLFIRI45%21%Fisher27Gefitinib/FOLFOX478%22%Hurwitz411I

FL35%（<2%412IFL/bevacizumab45%resection)Hoff21FOLFIRI/bevacizumab70%19%*OnepatientdeclinedofferedresectionUpdatedinformation

basedonFolprechtetal.AnnOncol,20052021/1/1231Liver-limiteddiseasePFSandRRinKRASwild-typeParameterFOLFIRI(n=32)Cetuximab+FOLFIRI(n=35)Hazard

/oddsratiop-valueMedianPFS(months)[95%CI]9.5[7.4–11.1]14.6[9.1–≥15]0.724[0.321–1.635]0.437Response(%)ORR[95%CI]50.0[31.9–68.1]77.1[59.9–89.6]

3.456[1.140–10.472]0.025aaCochran-Mantel-Haenszel(CMH)testVanCutsem,Köhneinpress2021/1/1232Randomizedmulticenterstudyofce

tuximabplusFOLFOXorcetuximabplusFOLFIRIinneoadjuvanttreatmentofnon-resectablecolorectallivermetastases(CEL

IMstudy)G.Folprecht,1T.Gruenberger,2J.T.etal◼Patientswithnon-resectablecolorectallivermetastases◼Noextrahepaticdisease2021/1/1233Efficacy

:ConfirmedResponseFOLFOX6+FOLFIRI+Allcetuximabcetuximabpatientsn=53n=53n=106CR/PR68%57%62%95%CI54-80%42-70%52-72%SD28%30%29%PD4%13%8%

Responsesconfirmedby2ndCTscanaccordingtoRECISTorbyresectionChisquaretestforcomparisonbetweenFOLFOX6+CetvsFOLFIRI+Cetwouldbe0.23KRASKRASEGFR

EGFRwild-typeMutantIHC+IHC-n=67n=28n=77n=29CR/PR70%43%60%69%95%CI58-81%24-63%48-71%49-85%2021/1/1234Rese

ctionsFOLFOX6+FOLFIRI+Allcetuximabcetuximabpatientsn=53n=53n=106R0resections38%30%34%R1-resect/Resect+RFA2%8%5%RFA9%6%8%R0/R1resect./RFA49%43%46%Tech

nically≥5liverKRASnon-resectablemetastaseswild-typen=57n=48n=67R0resections28%40%33%ComparisonofR0resectionsbetweenstrata

technicallynon-resectableand≥5livermets:p=0.142021/1/1235手术前化疗时限化疗时间❖最佳选择时间？2021/1/1236casesmobiditySinusoidaldistentionNeutrophilinfiltrateste

atosisfibrosischemo4538%22（48.8％）432519surgery2213.5%3（13.6％）22147P-value0.030.005NSNSNScyclesmorbidity%P≧613/2454<64/21190.047Moret

han6cyclesofneoadjuvantsystemicchemotherapyincreasemorbiditysignificantlyKarouietal.Annsurg.2006:243:1-7Therelationbetweendurationofpreoperativech

emotherapyandperioperativemorbidity2021/1/1237手术前化疗的关注问题化疗时间❖手术最佳时间？个体化！及时评估疗效，预防并发症不忘主题——手术治疗！2021/1/12

38谢谢！2021/1/1239谢谢