結(jié)直腸癌新輔助治療含肝轉(zhuǎn)移-1課件

直腸癌術(shù)前放化療.直腸癌術(shù)前放化療.1新輔助治療的目的提高手術(shù)切除率提高保肛率降低局部復(fù)發(fā)延長(zhǎng)患者無(wú)病生存期.新輔助治療的目的提高手術(shù)切除率.2推薦T3和/或N+的可切除直腸癌患者，推薦術(shù)前新輔助放化療。直腸癌術(shù)前化療推薦以氟尿嘧啶類藥物為基礎(chǔ)的化療方案.推薦T3和/或N+的可切除直腸癌患者，推薦術(shù)前新輔助放化療。3..4..5..6..7..8..9..10..11..12..13結(jié)腸癌肝轉(zhuǎn)移術(shù)前化療.結(jié)腸癌肝轉(zhuǎn)移術(shù)前化療.14推薦結(jié)直腸癌患者合并肝轉(zhuǎn)移，可切除或者潛在可切除，推薦術(shù)前化療或化療聯(lián)合靶向藥物治療：西妥昔單抗（推薦用于K-ras基因狀態(tài)野生型患者），或聯(lián)合貝伐珠單抗化療方案推薦FOLFOX，或者FOLFIRI，或者CapeOx，.推薦結(jié)直腸癌患者合并肝轉(zhuǎn)移，可切除或者潛在可切除，推薦術(shù)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…K?hneetal,AnnOncol2005.Resectionrateofmetastasesa17新輔助化療優(yōu)勢(shì)患者體內(nèi)化療藥物的藥敏試驗(yàn)清除微小轉(zhuǎn)移灶觀察甄別出快速進(jìn)展病例提高R0切除率？并減少切除的正常肝組織延長(zhǎng)生存期？.新輔助化療優(yōu)勢(shì)患者體內(nèi)化療藥物的藥敏試驗(yàn).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?高復(fù)發(fā)風(fēng)險(xiǎn)whichregimen?化療？HAI？方案？FU、OXA？Target？

.AdjuvantChemotherapyforCRC23EORTCphaseIIIstudy40983

研究設(shè)計(jì)RandomizeSurgeryFOLFOX4FOLFOX4Surgery6cycles(3months)6cycles(3months)364例潛在可切除肝轉(zhuǎn)移

(metachronousorsynchronous)，4個(gè)以上病灶，無(wú)肝外轉(zhuǎn)移.EORTCphaseIIIstudy40983

研究24EORTCStudy40983

CTSP3-yFPS%42.433.20.025.EORTCStudy4098325樂(lè)沙定，伊立替康和持續(xù)滴注5-FULV(FOLFOXIRI)兩周方案和Folfiri相比一線治療轉(zhuǎn)移性結(jié)直腸癌：III期臨床結(jié)果（GONO）A.Falcone,etal

ASCOGI2006,#227不能切除的結(jié)直腸癌肝轉(zhuǎn)移新輔助化療.樂(lè)沙定，伊立替康和持續(xù)滴注5-FULV(FOLFOXIRI)26伊立替康，樂(lè)沙定和持續(xù)滴注5-FULV(FOLFOXIRI)兩周方案和Folfiri相比一線治療轉(zhuǎn)移性結(jié)直腸癌：III期臨床結(jié)果（GONO）*DouillardLancet2000**MasiAnnOncol2004臨床設(shè)計(jì)FOLFIRI*RCPT-11 180mg/m21-hd.1L-LV 100mg/m22-hd.1,25FU 400mg/m2bolusd.1,25FU 600mg/m222-hd.1,2q.2wksx12個(gè)周期FOLFOXIRI**CPT-11 165mg/m21-hd.1LOHP 85mg/m22-hd.1L-LV 200mg/m22-hd.15FU 3200mg/m248-hCId.1q.2wksx12個(gè)周期分層

中心

PS0/1-2

輔助化療FOLFIRI方案進(jìn)展后，推薦含樂(lè)沙定的方案.伊立替康，樂(lè)沙定和持續(xù)滴注5-FULV(FOLFOXIRI)27A.Falcone,ASCOGI2006,#227*p<0.001有效率

(ITT分析)化療后手術(shù)切除率

(所有病人)*p<0.033療效結(jié)果主要目標(biāo)：RR次要目標(biāo)：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,K?hneinpress.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手術(shù)前化療時(shí)限化療時(shí)間最佳選擇時(shí)間？.手術(shù)前化療時(shí)限化療時(shí)間最佳選擇時(shí)間？.35Morethan6cyclesofneoadjuvantsystemicchemotherapyincreasemorbiditysignificantlyKarouietal.Annsurg.2006:243:1-7Therelationbetweendurationofpreoperativechemotherapyandperioperative