结直肠癌新辅助治疗含肝转移-1课件

直肠癌术前放化疗.直肠癌术前放化疗.1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.新辅助治疗的目的提高手术切除率.2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.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。3..4..5..6..7..8..9..10..11..12..13结肠癌肝转移术前化疗.结肠癌肝转移术前化疗.14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，.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15livermetastasesNotresectableresectablechemotherapy85%15%+otherlocationsofmetastaseschemotherapy50%50%Patientswithmetastaticcolorectalcancer5ySurvival:5%5ysurvival:5%Metastaticcolorectalcancer5ysurvival:20-40%.livermetastasesNotresectable16ResectionrateofmetastasesandtumorresponseStudiesincl.selectedpats.(livermetastasesonly,noextrahepat.disease)r=.96,p=.002Studiesincl.allpatientswithmetastaticCRC(solidline)r=.74,p<.001PhaseIIIstudiesinmetastaticCRC(dashedline)r=.67,p=.024,p=.024

Folprecht…Köhneetal,AnnOncol2005.Resectionrateofmetastasesa17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？.新辅助化疗优势患者体内化疗药物的药敏试验.18Adjuvant,neoadjuvant,conversiontherapyforCRClivermetastasesResectableadjuvantneo-adjuvantUnresectableConversionchemotherapy.Adjuvant,neoadjuvant,convers19ColorectalCaR0ResectionofMetastasesControversy:AdjuvantTherapy?USAYes

(KemenyNEJM1999)EuropaNo

(LorenzNEJM2000).ColorectalCaR0Resectiono20KemenyetalNEJM1999and2005Livermetastases:adjuvantHAI+i.v.CTXp=0.02Medianoverallsurvival Fong0-2 Fong3-5HAI+systemic 83.3mo 60.0mo

(10y:38.7%)systemic 82.8mo 38.3mo (10y:16.3%) p=0.13.KemenyetalNEJM1999and20021LV5FUvs.FOLFIRIasadjuvanttherapyfollowingresectionofCLM-DFS1-yearDFS:63%vs.77%2-yearDFS:46%vs.51%Ychouetal.ASCO2008.LV5FUvs.FOLFIRIasadjuvant22AdjuvantChemotherapyforCRClivermetastasesYES！Whichpatients?高复发风险whichregimen?化疗？HAI？方案？FU、OXA？Target？

.AdjuvantChemotherapyforCRC23EORTCphaseIIIstudy40983

研究设计RandomizeSurgeryFOLFOX4FOLFOX4Surgery6cycles(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.EORTCphaseIIIstudy40983

研究24EORTCStudy40983

CTSP3-yFPS%42.433.20.025.EORTCStudy4098325乐沙定，伊立替康和持续滴注5-FULV(FOLFOXIRI)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,etal

ASCOGI2006,#227不能切除的结直肠癌肝转移新辅助化疗.乐沙定，伊立替康和持续滴注5-FULV(FOLFOXIRI)26伊立替康，乐沙定和持续滴注5-FULV(FOLFOXIRI)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）*DouillardLancet2000**MasiAnnOncol2004临床设计FOLFIRI*RCPT-11 180mg/m21-hd.1L-LV 100mg/m22-hd.1,25FU 400mg/m2bolusd.1,25FU 600mg/m222-hd.1,2q.2wksx12个周期FOLFOXIRI**CPT-11 165mg/m21-hd.1LOHP 85mg/m22-hd.1L-LV 200mg/m22-hd.15FU 3200mg/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.伊立替康，乐沙定和持续滴注5-FULV(FOLFOXIRI)27A.Falcone,ASCOGI2006,#227*p<0.001有效率

(ITT分析)化疗后手术切除率

(所有病人)*p<0.033疗效结果主要目标：RR次要目标：PFS,OS,postsurgicalresectionsn,safetyQOL.A.Falcone,ASCOGI2006,#22728RescueSurgeryforUnresectableColorectalLiverMetastasesDownstagedbyChemotherapyAModeltoPredictLong-termSurvivalRetrospectivestudy1104caseswithunresectablelivermetastasesChemotherapyregimens：5-FU/LV/OXAorIRIorboth138(12.5%)achievedsecondarycurativehepaticresectionSurvivalrate:5-year33%10-year23%AdamRetal,Annsurg.2004;240:644-657.RescueSurgeryforUnresectabl29Resectionoflivermetastases:non-selectedpatientstreatedwithtargeted/cytotoxicagentsFirstauthor N Regimen RRResectionrate

Folprecht 21 Cetuximab/irinotecan 67% 19% /AIO (24%)*

DiazRubio 43 Cetuximab/FOLFOX4 79% 19%Rougier 42 Cetuximab/FOLFIRI 45% 21%

Fisher 27 Gefitinib/FOLFOX4 78% 22%Hurwitz 411 IFL 35% （<2% 412 IFL/bevacizumab 45%resection)Hoff 21 FOLFIRI/bevacizumab 70% 19%*OnepatientdeclinedofferedresectionUpdatedinformationbasedonFolprechtetal.AnnOncol,2005.Resectionoflivermetastases:30Liver-limiteddisease

PFSandRRinKRASwild-type

aCochran-Mantel-Haenszel(CMH)testVanCutsem,Köhneinpress.Liver-limiteddisease

PFSand31RandomizedmulticenterstudyofcetuximabplusFOLFOXorcetuximabplusFOLFIRIinneoadjuvanttreatmentofnon-resectablecolorectallivermetastases(CELIMstudy)G.Folprecht,1

T.Gruenberger,2

J.T.etalPatientswithnon-resectablecolorectallivermetastasesNoextrahepaticdisease.Randomizedmulticenterstudyo32Efficacy:ConfirmedResponseResponsesconfirmedby2ndCTscanaccordingtoRECISTorbyresectionChisquaretestforcomparisonbetweenFOLFOX6+CetvsFOLFIRI+Cetwouldbe0.23.Efficacy:ConfirmedResponse33ResectionsComparisonofR0resectionsbetweenstratatechnicallynon-resectableand≥5livermets:p=0.14.ResectionsComparisonofR0res34手术前化疗时限化疗时间最佳选择时间？.手术前化疗时限化疗时间最佳选择时间？.35Morethan6cyclesofneoadjuvantsystemicchemotherapyincreasemorbiditysignificantlyKarouietal.Annsurg.2006:243:1-7Therelationbetweendurationofpreoperativechemotherapyandperioperative