結(jié)直腸癌新輔助治療

結(jié)直腸癌新輔助治療結(jié)直腸癌新輔助治療結(jié)直腸癌新輔助治療直腸癌術(shù)前放化療22021/1/12直腸癌術(shù)前放化療2021/1/122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)延長患者無病生存期2021/1/123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2021/1/1242021/1/1252021/1/1262021/1/1272021/1/1282021/1/1292021/1/12102021/1/12112021/1/12122021/1/12132021/1/1214結(jié)腸癌肝轉(zhuǎn)移術(shù)前化療2021/1/1215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，2021/1/1216livermetastasesNotresectableresectablechemotherapy85%15%+otherlocationsofmetastaseschemotherapy50%50%Patientswithmetastaticcolorectalcancer5ySurvival:5%5ysurvival:5%Metastaticcolorectalcancer5ysurvival:20-40%2021/1/1217ResectionrateofmetastasesandtumorresponseStudiesincl.selectedpats.(livermetastasesonly,noextrahepat.disease)r=.96,p=.002Studiesincl.allpatientswithmetastaticCRC(solidline)r=.74,p<.001PhaseIIIstudiesinmetastaticCRC(dashedline)r=.67,p=.024,p=.024

Folprecht…K?hneetal,AnnOncol20052021/1/1218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生存期？2021/1/1219Adjuvant,neoadjuvant,conversiontherapyforCRClivermetastasesResectableadjuvantneo-adjuvantUnresectableConversionchemotherapy2021/1/1220ColorectalCaR0ResectionofMetastasesControversy:AdjuvantTherapy?USAYes

(KemenyNEJM1999)EuropaNo

(LorenzNEJM2000)2021/1/1221KemenyetalNEJM1999and2005Livermetastases: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=0.132021/1/1222LV5FUvs.FOLFIRIasadjuvanttherapyfollowingresectionofCLM-DFS1-yearDFS:63%vs.77%2-yearDFS:46%vs.51%Ychouetal.ASCO20082021/1/1223AdjuvantChemotherapyforCRClivermetastases

YES！

Whichpatients?

高復(fù)發(fā)風(fēng)險(xiǎn)

whichregimen?

化療？HAI？方案？FU、OXA？Target？

2021/1/1224EORTCphaseIIIstudy40983

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，無肝外轉(zhuǎn)移2021/1/1225EORTCStudy40983mobidityHepaticfailureBiliaryfistulableedingmotalitychemo24.5%6.4%5.5%2.7%0.9%surgery13.3%1.6%1.6%2.3%1.6%

CTSP3-yFPS%42.433.20.025手術(shù)情況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樂沙定，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2021/1/1227伊立替康，樂沙定和持續(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，推薦含樂沙定的方案2021/1/1228A.Falcone,ASCOGI2006,#227外部評(píng)估FOLFIRI

(122pts)FOLFOXIRI

(122pts)完全緩解6%7%部分緩解28%53%完全+部分95%可信區(qū)間34%0.25-0.4360%*0.51-0.68穩(wěn)定34%21%進(jìn)展24%11%不可評(píng)估8%8%*p<0.001有效率

(ITT分析)化療后手術(shù)切除率

(所有病人)FOLFIRI

(122pts)FOLFOXIRI

(122pts)RO6%

(7pts)15%*(18pts)R11%2%Explorative8%1%*p<0.033療效結(jié)果主要目標(biāo)：RR次要目標(biāo)：PFS,OS,postsurgicalresectionsn,safetyQOL2021/1/1229RescueSurgeryforUnresectableColorectalLiverMetastasesDownstagedbyChemotherapyAModeltoPredictLong-termSurvivalRetrospectivestudy1104caseswithunresectablelivermetastasesChemotherapyregimens：5-FU/LV/OXAorIRIorboth138(12.5%)achievedsecondarycurativehepaticresectionSurvivalrate:5-year33%10-year23%AdamRetal,Annsurg.2004;240:644-6572021/1/1230Resectionoflivermetastases:non-selectedpatientstreatedwithtargeted/cytotoxicagentsFirstauthor N Regimen

RR

Resectionrate

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,20052021/1/1231Liver-limiteddisease

PFSandRRinKRASwild-type

ParameterFOLFIRI(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,K?hneinpress2021/1/1232RandomizedmulticenterstudyofcetuximabplusFOLFOXorcetuximabplusFOLFIRIinneoadjuvanttreatmentofnon-resectablecolorectallivermetastases(CELIMstudy)G.Folprecht,1

T.Gruenberger,2

J.T.etalPatientswithnon-resectablecolorectallivermetastasesNoextrahepaticdisease2021/1/1233Efficacy:ConfirmedResponse

FOLFOX6+FOLFIRI+All

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

Responsesconfirmedby2ndCTscanaccordingtoRECISTorbyresectionChisquaretestforcomparisonbetweenFOLFOX6+CetvsFOLFIRI+Cetwouldbe0.23

KRASKRASEGFREGFR

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

FOLFOX6+FOLFIRI+All

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

Technically≥5liverKRAS

non-resectablemetastaseswild-typen=57n=48n=67R0resections28%40%33%ComparisonofR0resectionsbetweenstratatechnicall