胃癌青島梁軍詳解演示文稿

胃癌青島梁軍詳解演示文稿當(dāng)前1頁，總共64頁。（優(yōu)選）胃癌青島梁軍當(dāng)前2頁，總共64頁。全球每年:934000新患者，700000死亡，5年生存率20%

胃癌流行病學(xué)：亞太地區(qū)發(fā)病率高

ParkinDMetal.CACancerJClin2005;55:74–108YangL.WorldJGastroenterol.2006;12;17–2020/100000<10/1000001020/100000胃癌發(fā)病率Themajorityofgastriccancercases(42%)occurinChina當(dāng)前3頁，總共64頁。中國胃癌的發(fā)病率及死亡率

Incidence&MortalityofGCinChinaYangL.WorldJGastroenterol,2006當(dāng)前4頁，總共64頁。東西方胃癌的差異發(fā)生率

高低東亞西方食管胃結(jié)合部癌少多早期胃癌常見少見標(biāo)準(zhǔn)術(shù)式D2D0-1術(shù)后5年生存率50-70%<30%標(biāo)準(zhǔn)的輔助治療術(shù)后化療(S-1)術(shù)后放化療圍手術(shù)期化療ECF晚期胃癌的標(biāo)準(zhǔn)治療S-1+CDDPCape+CDDPECFDCF，EOX5當(dāng)前5頁，總共64頁。胃癌診治現(xiàn)狀手術(shù)：手術(shù)是胃癌最確切的治愈手段

手術(shù)率83.9%，切除率50.9%，根治性切除23.6%放療:放療可提高局部控制單純放療多用以姑息性治療，止血，緩解疼痛等。輔助放化療對于高危的II-IIIB期有生存率的提高，化療：可以提高生存，改善生活質(zhì)量生物靶向治療：新的希望當(dāng)前6頁，總共64頁。PatientreferralEndoscopicandpathologicaldiagnosisSURGERY目前中國胃癌治療的主要模式CurrentschemaofgastriccancermanagementItissolate,unresectable,gotochemotherapyHurry,takeittotheoperatingtableimmediately！當(dāng)前7頁，總共64頁。胃癌的流行病學(xué)氟尿嘧啶類藥物在胃癌中應(yīng)用胃癌的多學(xué)科綜合治療當(dāng)前8頁，總共64頁。RR

15%

20-30%23~72%

40%±1960’s1970-80’s1990’s20005-fu基礎(chǔ)ECF,LFEP5-FU+/-LV/PFAMTXEAP,FAPFUPFAMELFUFTM卡陪他濱,S-1紫杉烷奧沙利鉑CPT-11,靶向治療OS4-5m6-7m6m8±m(xù)

1991年，JCO報道了一項EORTC的III期臨床試驗研究結(jié)果，顯示FAMTX方案比FAM具有更高的有效率和生存優(yōu)勢，因此，F(xiàn)AMTX被許多學(xué)者推薦為當(dāng)時的標(biāo)準(zhǔn)方案。DDP1993年ECF和FAMTX方案比較，中位生存時間、客觀有效率更佳。在歐洲，ECF方案被認(rèn)為是進(jìn)展期胃癌化療的標(biāo)準(zhǔn)方案。但是，該方案中因為表阿霉素有心臟毒性，其應(yīng)用有很多爭議。1997年CF與FAM及5-FU比較，CF方案的結(jié)果并不亞于ECF方案，且沒有阿霉素帶來的毒副反應(yīng)。許多亞洲和美國學(xué)者更傾向于選擇CF作為推薦方案。胃癌的化療歷程1980年JohnSMacdonald博士最先證實了FAM方案的有效性：可以使進(jìn)展期胃癌患者的中位生存期達(dá)到5.5個月，且耐受性好,一度成為金標(biāo)準(zhǔn)當(dāng)前9頁，總共64頁。氟尿嘧啶類藥物的發(fā)展歷程1950196019701980199020005-FUHeidelberger1957TegafurSynthesizedin1967UFTFirstApprovedinJapan1983S-1Developed’90CapecitabineApprovedbyFDA1998FurtulonSynthesizedin19765-FUIVRoche,1962FurtulonApprovedinJapan1987腫瘤選擇性,口服腫瘤內(nèi)激活/口服靜脈非腫瘤選擇性,口服當(dāng)前10頁，總共64頁?？ㄅ闼麨IS-1CPT-11紫杉烷奧沙利鉑靶向治療當(dāng)前11頁，總共64頁。熱點問題：希羅達(dá)是否能替代5-FU當(dāng)前12頁，總共64頁。REAL-2:首個食管-胃的III期

藥物臨床研究Cunninghametal.NewEngJMed2008Epirubicin50mg/m2day1Cisplatin60mg/m2vsoxaliplatin130mg/m2

day15-FU200mg/m2/daycontinuousinfusionvsCapecitabine500–625mg/m2

twicedailycontinuousFor24weeks:eightcyclesevery3weeks

Epirubicin

Cisplatin5-FU

Epirubicin

Oxaliplatin5-FUEpirubicinCisplatinXelodaEpirubicinOxaliplatinXelodaR主要研究目的:OS2X2組研究設(shè)計

，

ECF作為標(biāo)準(zhǔn)對照組一線治療進(jìn)展期胃癌及食道胃接合部癌當(dāng)前13頁，總共64頁。12Months2430.20.01.00REAL-2:EOX組的總生存明顯高于ECF組HR=0.80(95%CI:0.66–0.97)

Log-rankp=0.0211.29.9EOX (n=244)ECF (n=263)概率ITTpopulationCunninghametal.NEJM2008當(dāng)前14頁，總共64頁。ML17032治療直至進(jìn)展主要終點:PFS非劣效既往未治療的進(jìn)展期胃癌n=316隨機(jī)卡培他濱(1000mg/m2bdD1-14)/順鉑(80mg/m2D1)(XP)q3w5-FU(800mg/m2/dayD1-5)/順鉑(80mg/m2D1)(FP)q3wEstimatedprobabilityHR=0.81(95%CI:0.63–1.05)HRupperlimit<1.250PFS/Months24681012141618202224261.00.20.0XP(n=139)FP(n=137)Kangetal.AnnOncol2009當(dāng)前15頁，總共64頁。卡培他濱為基礎(chǔ)的方案較5-FU為基礎(chǔ)的方案均具有生存優(yōu)勢，死亡風(fēng)險下降13％PS0-1PS1Age<60Age≥60局部進(jìn)展期組轉(zhuǎn)移組Overalleffect0.400.500.600.700.800.901.0001.40CapecitabinebetterHazardRatio5FUbetterOkines,etal.annalsofoncology2009MayMeta-analysisoftheREAL2andML17032當(dāng)前16頁，總共64頁。

卡培他濱成為胃癌治療的新標(biāo)準(zhǔn)：

MarkusMoehler,Multidisciplinarymanagementofgastricandgastroesophagealcancers；WorldJGastroenterol2008June28;14(24):3773-3780各種抗體及信號傳導(dǎo)抑制劑藥物以卡培他濱作為基礎(chǔ)化療當(dāng)前17頁，總共64頁。胃癌的流行病學(xué)氟尿嘧啶類藥物在胃癌中應(yīng)用胃癌的多學(xué)科綜合治療當(dāng)前18頁，總共64頁。Surgery-orientedTreatmentModelSurgicalexplorationfirstGenerallytotalorsubtotalgastrectomywithorwithoutsystemiclymphnodedissectionAdjuvantchemotherapyforallSupportivecareformetastaticdiseases當(dāng)前19頁，總共64頁。SurgicalExplorationBeijingCancerHospital(1995-2005):n=2312ExplorationGastrostomyorileostomyOthersTotal3644686當(dāng)前20頁，總共64頁。Whatcanwedonow?Lookingbackwardtofindwhatisnotsoperfect……當(dāng)前21頁，總共64頁。胃癌不同分期外科治療的地位不同GCMetastasisandTreatmentNEMRSN,WedgeD2gastrectomyD2+ChemoHPAnysurgeoncancureNosurgeoncancureSurgeon-dependent當(dāng)前22頁，總共64頁。SurgeonOncologistSurgeonOncologistRadiationoncologistSurgeonOncologistRadiationoncologistPathologistsRadiologistsNursing……目前推崇而且很活躍的治療模式-MDTActiveInvolvement當(dāng)前23頁，總共64頁。PatientReferralConfirmatoryDiagnosisStagingDiagnosisDataCollectionMDTDecisionMaking當(dāng)前24頁，總共64頁。多學(xué)科的綜合治療較單純手術(shù)治療可明顯改善患者的生存預(yù)后！當(dāng)前25頁，總共64頁。WecanfindthatCombinedmodalitytherapyiseffectiveforpatientswithlocalizedgastriccancer.MDTforgastriccancermanagementworldwideiswarranted.當(dāng)前26頁，總共64頁。SurgeryremainsthemostimportanttreatmentforGCAdequatemarginofcompleteresectionhasbecomethebasicprinciplesofradicalgastrectomyLymphadenectomyPrimarytumorresection當(dāng)前27頁，總共64頁。Portalsystem-LiverFromSanoT.2007當(dāng)前28頁，總共64頁。PeritonealseedingFromSanoT.2007當(dāng)前29頁，總共64頁。Lymphaticsystem–SystemiccirculationFromSanoT.2007當(dāng)前30頁，總共64頁。D0/D1D2RegionalnodemetastasisFromSanoT.2007當(dāng)前31頁，總共64頁。LymphadenectomyforGastricCancerD0D1D2當(dāng)前32頁，總共64頁。TheMRCRandomizedSurgicalTrial.研究病例: StageI-III胃癌

(UICCTNMCancerStage)總生存情況（胃癌相關(guān)死亡）CuschieriAetal.BrJCancer79:1522-1530,1999兩組間并未看到明顯的生存差異當(dāng)前33頁，總共64頁。DutchD1D2trial共1078例患者入組，其中711例（D1組381例；D2組331例）納入研究D1=standardizedlimitedlymphadenectomy.D2=standardizedextendedlymphadenectomy.IlfetSongun,etal.LancetOncol2010;11:439–4915-YEAROVERALLSURVIVALD1:21%(85of380,95%CI17–26);D2:29%(98of331,24–34)(P=0.34).15years’Overallsurvival當(dāng)前34頁，總共64頁。死亡原因胃癌相關(guān)死亡D1組的胃癌相關(guān)死亡率顯著高于D2組（P=0.01）DutchD1D2trialIlfetSongun,etal.LancetOncol2010;11:439–49當(dāng)前35頁，總共64頁?；颊邚?fù)發(fā)、轉(zhuǎn)移情況D2組的局部復(fù)發(fā)及區(qū)域復(fù)發(fā)率均顯著低于D1組，而兩組從隨訪2.5年開始體現(xiàn)出這種趨勢（40of330[12%]vs82of380[22%]；37of330[11%]vs65of380[17%]）DutchD1D2trialIlfetSongun,etal.LancetOncol2010;11:439–49當(dāng)前36頁，總共64頁。胃癌的根治性淋巴結(jié)清掃D0D1D2淋巴結(jié)清掃范圍在國際上仍有爭論但已開始逐步達(dá)成共識胃癌根治術(shù)應(yīng)在大規(guī)模的腫瘤中心由有經(jīng)驗的外科醫(yī)生完成，同時需包括區(qū)域淋巴結(jié)——胃周淋巴結(jié)清掃（D1），以及伴隨腹腔干具名血管的淋巴結(jié)（D2）?！狽CCN胃癌指南v2010.2當(dāng)前37頁，總共64頁。PerioperativechemothrapyNEnglJMed(2006)355(1):11–20PFSOS當(dāng)前38頁，總共64頁。MAGICtrial

CurrentControlledTrialsnumberISRCTN93793971

RandomlyAssignedPatientsWithResectableAdenocarcinomaStomachEsophagogastricJunctionLowerEsophagusTherapyPerioperativeChemotherapy&Surgery(250Patients)SurgeryAlone(253Patients).ChemotherapyThree

PreoperativeCyclesofECFThreePostoperativeCyclesofECFMedianFollow-up

of4YearsThePrimaryEndPointWasOverallSurvival當(dāng)前39頁，總共64頁。MAGICtrial

CurrentControlledTrialsnumberISRCTN93793971

ThePerioperative-chemotherapyGrouphad

aHigherlikelihoodofOverallSurvival&Progression-free

SurvivalOverallSurvival(OS)HazardRatioForDeath,

0.7595%ConfidenceInterval,0.60To0.93;P=0.009Five-yearSurvivalRate,36PercentVs.23PercentProgression-free

Survival(PFS)HazardRatioForProgression,0.6695%Confidence

Interval,0.53To0.81;P<0.001當(dāng)前40頁，總共64頁。5-FU/LVfor5daysRadiation45Gy+5-FU/LV5-FU/LVfor5daysX2SurgeryaloneStageIB~IVM0R0resectionn=556進(jìn)展期胃癌術(shù)后輔助放化療研究（美國）IntergroupStudyINT-0116Macdonaldetal.NEnglJMed2001;345:731-8當(dāng)前41頁，總共64頁。AdjuvantChemoradiation:INT0116當(dāng)前42頁，總共64頁。TheimportanceofcurativesurgerynecessitatesneoadjuvantchemotherapyforadvancedgastriccancerSurvivalcurveofdifferentsurgeryofgastriccancerpatients(Kaplan-meiermethod)0:curativeresection;1:palliativeresection(p<0.05)當(dāng)前43頁，總共64頁。FromAugust2005toDecember2007,193eligiblepatientswererecruited,NACT105casesMulticenterClinicaltrialsonNeoadjuvantChemotherapyinBeijing,ChinaPI:ProfessorJiafuJi,M.D.OrganizedbyChineseSurgicalAssociation&ChineseAnticancerAssociation8largehospitalsenrolledinthisstudyStudygroup:Oxaliplatin/CF/5-FuTime:2005-2007Oxaliplatinand5-flurouracil/leucovorin(FOLFOX7)asPerioperativeTreatmentversusAdjuvantAloneinLocallyAdvancedResectableGastricCancer:BJSA-01StudyDesignandInteriumResults.JiJF,LiZY,WuAW,LiuYH,ZhangZT,WangS,YeYJ,LiR,LiZXASCOGImeeting2007當(dāng)前44頁，總共64頁。新輔助化療的優(yōu)勢

AdvantageofNeoadjuvantchemotherapyNACincreasestheR0resectionratebyshrinkageofthemetastaticnodesandprimarytumor.PostAdjuvantChemo(PACx)showsusuallylowercomplianceduetohighmorbidity,mainlycausedbycombinedresectionofpancreasforadvancedcases,andweaknessandchangeofdigestiveorganfunctionaftergastrectomywhichoftencausedifficultyoforalintakeandappetiteloss. NACshowshighcompliance.Earlytreatmentofmicrometastasisindistantsitemayimprovesurvival.當(dāng)前45頁，總共64頁。

多學(xué)科綜合治療當(dāng)前46頁，總共64頁。術(shù)后化療多學(xué)科治療胃癌術(shù)前化療手術(shù)術(shù)前放化療手術(shù)食管-胃交界腫瘤術(shù)前化療手術(shù)術(shù)后化療手術(shù)術(shù)后放化療手術(shù)當(dāng)前47頁，總共64頁。多學(xué)科治療胃癌術(shù)前化療手術(shù)食管-胃交界腫瘤當(dāng)前48頁，總共64頁。病變局限的食管癌和食管-胃交界腫瘤的術(shù)前化療OEO2手術(shù)術(shù)前化療5-FU/Cisplatin兩個周期，然后手術(shù)n=400n=402USIntergroup113手術(shù)術(shù)前化療5-FU/Cisplatin三個周期，然后手術(shù)，再續(xù)以兩個周期術(shù)后化療n=216n=227MRCLancet2002AllumetalJClinOncol2009KelsenetalNEJM1996JCO2007當(dāng)前49頁，總共64頁。長期總生存p=NSOEO2USIntergroup113AllumetalJCO2009;KelsenetalJCO2007中位隨訪:6years中位隨訪:8.8yearsp=0.03當(dāng)前50頁，總共64頁。基于個體患者資料的術(shù)前化療meta分析ThirionetalASCO2007當(dāng)前51頁，總共64頁。多學(xué)科治療胃癌術(shù)前化療手術(shù)術(shù)前放化療手術(shù)食管-胃交界當(dāng)前52頁，總共64頁。食管-胃交界處腺癌

術(shù)前化療

vs.術(shù)前放化療：

德國POET研究

術(shù)前化療 術(shù)前放化療病例數(shù) 64 62pCR 2% 15.6%總生存中位 21.1months 33.1months3-year 27.7% 47.4%局部腫瘤無進(jìn)展率3-year 59% 76.5%住院期間死亡率

3.8% 10.2%StahletalJClinOncol2009當(dāng)前53頁，總共64頁。StahletalJClinOncol2009HR:0.67;95%CI:0.41,1.07;p=0.1食管-胃交界處腺癌

術(shù)前化療

vs.術(shù)前放化療：

德國POET研究當(dāng)前54頁，總共64頁。多學(xué)科治療胃癌術(shù)前化療手術(shù)術(shù)前放化療手術(shù)食管-胃交界腫瘤手術(shù)術(shù)后化療當(dāng)前55頁，總共64頁。胃癌術(shù)后輔助治療的Meta分析作者 雜志 納入

病例數(shù)

死亡的Oddsratio

研究數(shù)

(95%CI)Hermans(1993) JClinOncology 11 2,096 0.88(0.78-1.08)Earle(1999) EurJCancer 13 1,990 0.80(0.66-0.97)Mari(2000) AnnOncology 20 3,658 0.82(0.75-0.89)Janunger(2002) EurJSurg 21 3,962 0.84(0.74-0.96)Panzini(2002) Tumori 17 3,118 0.72(0.62-0.84)Zhao(2008) CancerInvest 15 3,212 0.90(0.84-0.96)當(dāng)前56頁，總共64頁。SunetalBrJSurg2009胃癌術(shù)后輔助治療的Meta分析當(dāng)前57頁，總共64頁。胃癌術(shù)后S1單藥輔助化療—III期臨床隨機(jī)對照研究（ACTS-GC，日本）1059例(stageII/III，D2)隨訪3年S-1單藥組529casesOS:80.1%OS:70.1%單純手術(shù)組530cases備注：S-1治療12個月，80mg/m2/dx4周,休息2周；78%的病例完成了6個月治療，71%完成了12個月

3/4度毒性反應(yīng)少見(惡心、腹