NCCN胃癌指南解讀講義課件

NCCN胃癌臨床實(shí)踐指南中國(guó)版

解讀北京大學(xué)臨床腫瘤學(xué)院北京腫瘤醫(yī)院消化內(nèi)科沈琳2008腫瘤學(xué)臨床實(shí)踐指南（中國(guó)版）2008年第一版胃癌NCCN胃癌臨床實(shí)踐指南中國(guó)版

解讀1Copyright?2005AmericanCancerSocietyAge-standardizedIncidenceRatesforStomachCancerinworld.FromParkin,D.M.etal.CACancerJClin2005;55:74-108.世界胃癌年齡調(diào)整發(fā)病率Copyright?2005AmericanCance2對(duì)1990-1992年中國(guó)的1/10萬(wàn)人口死因抽樣調(diào)查資料中胃癌死亡情況進(jìn)行分析胃癌粗死亡率(crudemortalityrate)25.2/10萬(wàn)（M：32.8/10萬(wàn)，F(xiàn)：17.0/10萬(wàn)），占全部惡性腫瘤死亡的23.2%，惡性腫瘤死亡中第一位。（男性是女性1.9倍）中國(guó)胃癌世界人口調(diào)整死亡率(mortalityratesadjustedbytheworldpopulation)男性：40.8/10萬(wàn)，女性：18.6/10萬(wàn)，分別是歐美發(fā)達(dá)國(guó)家的4.2-7.9倍，3.8-8.0倍有明顯的地區(qū)差異和城鄉(xiāng)差別。全國(guó)抽樣調(diào)查263個(gè)點(diǎn)，胃癌調(diào)整死亡率在2.5-153.0/10萬(wàn)之間，Urbanareas:15.3/10萬(wàn);Ruralareas:24.4/10萬(wàn)，是城市的1.6倍對(duì)1990-1992年中國(guó)的1/10萬(wàn)人口死因抽樣調(diào)查資料中3NCCN共識(shí)分類(lèi)1類(lèi)：基于高水平的證據(jù)，NCCN達(dá)成共識(shí)，推薦應(yīng)用2A類(lèi)：基于包括臨床經(jīng)驗(yàn)在內(nèi)的稍低水平證據(jù)，NCCN達(dá)成共識(shí)，推薦應(yīng)用。2B類(lèi)：基于包括臨床經(jīng)驗(yàn)在內(nèi)的稍低水平證據(jù)，NCCN未達(dá)成統(tǒng)一共識(shí)（但無(wú)較大分歧）。3類(lèi)：NCCN對(duì)該建議的適宜性存在較大分歧。除非特別說(shuō)明，本指南中所有的建議均達(dá)成2A類(lèi)共識(shí)。NCCN共識(shí)分類(lèi)1類(lèi)：基于高水平的證據(jù)，NCCN達(dá)成共識(shí)，推4NCCN胃癌臨床實(shí)踐指南

2008第1版指南更新主要變化總結(jié)（GAST-1）：workup：PET/CT掃描和EUS作為可選的檢查項(xiàng)目。（GAST－2）：要求多學(xué)科會(huì)議討論患者所有三個(gè)治療途徑的抉擇T2以上分期患者將術(shù)前化療作為一類(lèi)推薦首選治療手段。術(shù)前放化療作為2B類(lèi)的首選治療手段。（GAST－3）：R0術(shù)后分期T2N0M0及以上者，如術(shù)前采用ECF方案化療，術(shù)后可選擇ECF繼續(xù)（1類(lèi)）（GAST－5）：followup：近端胃大部或全胃切除者，應(yīng)監(jiān)測(cè)并補(bǔ)充VitB12（GAST－A）：增加綜合治療模式原則新頁(yè)（GAST－B、C）：更新外科及系統(tǒng)化療原則（GAST－A）：新增放療原則新頁(yè)NCCNguidelines----GastricCancerChineseversion1.2008在整個(gè)治療指南中將chemotherapy/RT更改為chemoradiation將salvage改為palliativeNCCN胃癌臨床5與2007版類(lèi)似注意：除了特別指出的情況，所有推薦的治療都是2A證據(jù)的。臨床試驗(yàn)：NCCN認(rèn)為對(duì)于任何一個(gè)腫瘤病人參加臨床實(shí)驗(yàn)都獲得最佳治療.要特別鼓勵(lì)參與臨床試驗(yàn)。與2007版類(lèi)似注意：6強(qiáng)調(diào)多學(xué)科評(píng)估和協(xié)作！強(qiáng)調(diào)多學(xué)科評(píng)估和協(xié)作！7多學(xué)科綜合治療模式有益于局部進(jìn)展期胃癌患者（1類(lèi)證據(jù)）NCCN專(zhuān)家組基本觀點(diǎn)：不鼓勵(lì)單一學(xué)科成員單方面進(jìn)行治療決策。具備以下條件，可能給局部進(jìn)展期胃癌患者以最佳的綜合治療：例會(huì)形勢(shì)實(shí)用（一周或2周一次），相關(guān)學(xué)科的機(jī)構(gòu)和個(gè)人定期來(lái)共同回顧患者的詳細(xì)資料。每次例會(huì)，各相關(guān)學(xué)科都要積極參與，包括腫瘤外科，腫瘤內(nèi)科，消化科，放射科，病理科。此外，最好還能包括營(yíng)養(yǎng)科，社工，護(hù)理以及其他支持學(xué)科。所有長(zhǎng)期的治療策略要在全面分期檢查完成后再進(jìn)行，最好在所有治療開(kāi)始之前。決策前共同回顧原始的醫(yī)學(xué)數(shù)據(jù)而非單純閱讀報(bào)告。多學(xué)科團(tuán)隊(duì)做出共識(shí)推薦并摘要記錄在案，對(duì)每位患者是有益的。特定患者的主要治療小組或醫(yī)生應(yīng)尊重以及考慮多學(xué)科團(tuán)隊(duì)所做出的共識(shí)推薦。反饋部分患者的治療隨訪(fǎng)結(jié)果，對(duì)整個(gè)多學(xué)科團(tuán)隊(duì)是有效的實(shí)例教育方式。在例會(huì)期間，正式的定期復(fù)習(xí)相關(guān)文獻(xiàn)，對(duì)整個(gè)多學(xué)科團(tuán)隊(duì)是高效的教育方式。多學(xué)科綜合治療模式有益于局部進(jìn)展期胃癌患者（1類(lèi)證據(jù)）8NCCN胃癌指南解讀講義課件9分期CT掃描±EUS判斷病灶范圍腹腔鏡有助于部分患者的分期不能根治性切除標(biāo)準(zhǔn)局部進(jìn)展期:3/4站淋巴結(jié)轉(zhuǎn)移,大血管受侵或被包繞遠(yuǎn)處轉(zhuǎn)移或腹膜種植(包括腹腔脫落細(xì)胞學(xué)陽(yáng)性可切除腫瘤T1者在有經(jīng)驗(yàn)者可采用內(nèi)鏡下胃粘膜切除T1-T3合適的腫瘤切緣≥4cm（5cm）,鏡下陰性推薦D1/D2淋巴結(jié)清掃,應(yīng)至少檢查15個(gè)淋巴結(jié)，并結(jié)合位置清掃到2站淋巴結(jié)

T4應(yīng)切除受累部位不做常規(guī)脾切除,除非脾臟受累或脾門(mén)受侵可考慮留置空腸營(yíng)養(yǎng)管姑息手術(shù)可以接受切緣陽(yáng)性，淋巴結(jié)不強(qiáng)求清掃胃腸短路或營(yíng)養(yǎng)管外科治療原則NCCNv.1.2008GastricCancer分期外科治療原則NCCNv.1.200810結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期11JapaneseGastriccancerassociati（JGCA)腹腔細(xì)胞學(xué)（CY）CY0腹腔細(xì)胞學(xué)良性或無(wú)法確定CY1腹腔細(xì)胞學(xué)未見(jiàn)癌細(xì)胞CYx未作其它遠(yuǎn)處轉(zhuǎn)移（M）§M0腹膜、肝、腹腔細(xì)胞學(xué)外無(wú)遠(yuǎn)處轉(zhuǎn)移M1腹膜、肝、腹腔細(xì)胞學(xué)外有遠(yuǎn)處轉(zhuǎn)移Mx不清楚分期

表2日本胃癌學(xué)會(huì)（JGCA）分期（1998年第13版*）原發(fā)腫瘤（T）T1腫瘤侵犯粘膜層和/或粘膜肌層(M)和/或粘膜下層(SM)T2腫瘤侵犯固有肌層(MP)或漿膜下層(SS)?T3腫瘤穿透漿膜(SE)?T4腫瘤侵犯鄰近結(jié)構(gòu)(SI)?Nx不明局部淋巴結(jié)（N）淋巴結(jié)分站分組（見(jiàn)ST-3）淋巴結(jié)轉(zhuǎn)移程度N0無(wú)淋巴結(jié)轉(zhuǎn)移證據(jù)N1第一站淋巴結(jié)有轉(zhuǎn)移，第二、三站淋巴結(jié)無(wú)轉(zhuǎn)移N2第二站淋巴結(jié)有轉(zhuǎn)移，第三站淋巴結(jié)無(wú)轉(zhuǎn)移N3第三站淋巴結(jié)有轉(zhuǎn)移Nx區(qū)域淋巴結(jié)無(wú)法評(píng)估肝轉(zhuǎn)移（H）H0無(wú)肝轉(zhuǎn)移H1有肝轉(zhuǎn)移Hx不清楚腹膜轉(zhuǎn)移（P）P0無(wú)腹膜轉(zhuǎn)移P1有腹膜轉(zhuǎn)移*本分期源自JapaneseGastricCancerAssociation.JapaneseClassificationofGastricCarcinoma-2ndEnglishEdition.GastricCancer(1998)1:10–24?腫瘤可以穿透固有肌層達(dá)胃結(jié)腸韌帶或肝胃韌帶或大小網(wǎng)膜，但沒(méi)有穿透這些結(jié)構(gòu)的臟層腹膜。在這種情況下，原發(fā)腫瘤的分期為T(mén)2。如果穿透覆蓋胃韌帶或網(wǎng)膜的臟層腹膜，則應(yīng)當(dāng)被分為T(mén)3期。?腫瘤侵犯大、小網(wǎng)膜、食管和十二指腸不作為T(mén)4,經(jīng)胃壁內(nèi)擴(kuò)展至十二指腸或食管的腫瘤分期取決于包括胃在內(nèi)的這些部位的最大浸潤(rùn)深度?！霱1的種類(lèi)應(yīng)注明：LYM:淋巴結(jié)；PLE:胸膜；MAR:骨髓；OSS:骨；BRA:腦；MEN:腦膜；SKI:皮膚；OTH:其它N0N1N2N3T1IAIBIIIIIAT2IBIIIIIAT3IIIIIAIIIBT4IIIAIIIBIVH1,P1,CY1,M1JapaneseGastriccancerassoci12RegionalLNGroupAccordingtoLocationofTumorD14d4d4d653D211p12a14v1998a97LD/LRegionalLNGroupAccordingto13Sasakoetal:thelong-termoutcomeofsurvival：D2vsD2+,

nostatisticallysignificantdifference69%vs70%,p=0.57,HR:1.03,(95%CI:0.77-1.37).

SasakoM,SanoT,YamamotoS,etal.RandomizedphaseIIItrialofstandardD2versusD2+para-aorticlymphnode(PAN)dissection(D)forclinicallyM0advancedgastriccancer:JCOG9501.JClinOncol2006.24(18S):LBA4015.擴(kuò)大根治orD2?——循證醫(yī)學(xué)證據(jù)Sasakoetal:擴(kuò)大根治orD2?—14AprospectiverandomizedcontrolledclinicaltrialinTaiwan:D2vsD15-yearsurvivalD2dissectionwassuperiortoD1dissection

59.5%vs53.6%,p=0.041;HR:0.49,p=0.002

WuCW,HsiungCA,LoSS,etal.Nodaldissectionforpatientswithgastriccancer:Arandomizedcontrolledtrial.LancetOncol2006;7:309-315進(jìn)一步的臨床試驗(yàn)，特別是觀察手術(shù)前后的輔助治療應(yīng)該基于D2式手術(shù)！D1orD2?——循證醫(yī)學(xué)證據(jù)Aprospectiverandomizedcontr15適合于所有胃癌胃切除標(biāo)本原發(fā)性胃癌胃切除標(biāo)本的檢查原發(fā)性腫瘤*外科切緣評(píng)估?淋巴結(jié)評(píng)估?原發(fā)性胃癌的組織學(xué)類(lèi)型§Lauren分類(lèi)，1965日本胃癌研究協(xié)會(huì)（JRSGC）分類(lèi)，1981WHO分類(lèi)，2000病理學(xué)分期（pTNM）應(yīng)包括下列參數(shù)：腫瘤的惡性程度（分級(jí)）ξ浸潤(rùn)的深度淋巴結(jié)的部位、數(shù)目及陽(yáng)性數(shù)遠(yuǎn)端及近端外科切緣狀況注釋胃癌原發(fā)腫瘤檢查應(yīng)包括：腫瘤在胃粘膜確切位置及腫瘤范圍；腫瘤距近端和遠(yuǎn)端外科切緣的距離；腫瘤大體形態(tài)，包括腫瘤大小、早期胃癌的形態(tài)類(lèi)型；腫瘤切面，浸潤(rùn)胃壁情況。?外科切緣評(píng)估：胃切除標(biāo)本有遠(yuǎn)端及近端切緣：部分切除標(biāo)本，遠(yuǎn)端切緣是十二指腸，近端切緣是胃體；全胃切除標(biāo)本，遠(yuǎn)端切緣是十二指腸，近端切緣是食管。外科切緣有3種情況：R0：外科切緣干凈；R1：外科切緣鏡下陽(yáng)性；R2：外科切緣肉眼陽(yáng)性。建議切除的近端切緣應(yīng)距腫瘤邊緣5cm，同時(shí)應(yīng)常規(guī)術(shù)中切緣冰凍檢查。?淋巴結(jié)評(píng)估：見(jiàn)ST-1/2/3。根據(jù)胃切除時(shí)淋巴結(jié)清掃的范圍分為：D0：淋巴結(jié)清掃的范圍不包括所有N1淋巴結(jié)；D1：淋巴結(jié)清掃的范圍不包括所有N2淋巴結(jié)；D2：淋巴結(jié)清掃的范圍不包括所有N3淋巴結(jié)。按照AJCC標(biāo)準(zhǔn)，因?yàn)楸粰z查淋巴結(jié)的數(shù)量和淋巴結(jié)陽(yáng)性率之間有正相關(guān)，應(yīng)檢查至少15個(gè)淋巴結(jié)?！煳赴┙M織學(xué)類(lèi)型Lanren分類(lèi)（1965）：腸型；彌漫型JRSGC分類(lèi)（1981）：乳頭狀型管狀型低分化型 粘液型印戒細(xì)胞型WHO分類(lèi)（2000）腺癌腸型彌漫型乳頭狀腺癌管狀腺癌粘液腺癌印戒細(xì)胞癌腺鱗癌鱗狀細(xì)胞癌小細(xì)胞癌未分化癌其它ξ胃腺癌組織學(xué)分級(jí)：高分化；中分化；低分化；未分化病理學(xué)分期（pTNM）病理學(xué)分期與胃癌預(yù)后極其相關(guān)，早期胃癌預(yù)后極好，5年生存率達(dá)90%。建議使用AJCC/UICC分類(lèi)，在病理報(bào)告中N分期可增加標(biāo)注JRSGC要求的淋巴結(jié)部位。病理診斷原則適合于所有胃癌胃切除標(biāo)本注釋§胃癌組織學(xué)類(lèi)型病理診斷原則16系統(tǒng)化療原則NEW遵照原始文獻(xiàn)報(bào)道的藥物劑量/方案,合理用藥并進(jìn)行適當(dāng)調(diào)整患者合適的器官功能和體力狀況充分考慮化療的毒性和益處,并始終與患者及家屬討論/交流,并進(jìn)行患者教育,警示并防治不良反應(yīng),避免嚴(yán)重合并癥及縮短持續(xù)時(shí)間患者化療期間仔細(xì)觀察,及時(shí)治療合并癥,并適當(dāng)監(jiān)測(cè)患者血液學(xué)改變化療階段及時(shí)評(píng)估療效和長(zhǎng)期合并癥系統(tǒng)化療原則NEW遵照原始文獻(xiàn)報(bào)道的藥物劑量/方案,合172007.v.22008.v.1Preoperativechemo-therapyECFcategory1ECFcategory1ECFmodificationcategory1Preoperativechemo-radiationfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BTaxanes-based2BIrinotecan-based2Bpaclitaxel/Docetaxel+fluoropyrimidine(5FU/capecitabine）category2BUpdateof2008.v.1NCCNversion2007.v.22008.v.1Preoperativec18可切除胃癌圍手術(shù)期化療

---MAGICtrial胃癌（占85%）或低位食管癌（15%）ECF*3cs-手術(shù)-ECF3cs單一手術(shù)N=2505Y38%N=2535Y23%ECF:E50mg/m2C60mg/m2FU200mg/m2/dcivD.Cuuningham2005ASCOabs4001Cunninghametal,NEJM2006可切除胃癌圍手術(shù)期化療

---MAGICtrial胃癌（占19Chemo+SurgerySurgeryPatients250253Age6262ToSurgery219(88%)240(95%)PtswithR0resection169(68%)*166(66%)*Nopathologiccompleteresponses可切除胃癌圍手術(shù)期化療

---MAGICtrialCunninghametal,NEJM2006Chemo+SurgerySurgeryPatients20Chemo+SurgerySurgeryPathSize3.1cm5.0cm(p=0.001)T1/T2T3/T452%48%38%62%(p=0.009)N0/1N2/384%16%76%24%(p=0.01)Cunninghametal,NEJM2006可切除胃癌圍手術(shù)期化療

---MAGICtrialChemo+SurgerySurgeryPathSiz21OverallSurvivalPatientsatriskLogrankp-value=0.009HazardRatio=0.75

(95%CI0.60-0.93)CSCS250168111795238272531558050311890.00.10.20.30.40.50.60.70.80.91.0Monthsfromrandomization0122436486072149250170253EventsTotalCSCSSurvivalrateOverallSurvivalPatientsatri22可切除胃癌圍手術(shù)期化療

5-FU+DDPinAGC/LE---FFCD9703trialFP2～3cs（98例）-手術(shù)-FP2～3cs(RR+SDn+)（54例）單一手術(shù)N=1135YDFS34%N=1115YDFS21%FP:5-FU800mg/m2d1-5ciDDP100mg/m2d1Q4w隨訪(fǎng)5.7Y賁門(mén)、胃89％食管11％可切除胃癌圍手術(shù)期化療

5-FU+DDPinAGC/L23可切除胃癌圍手術(shù)期化療

5-FU+DDPinAGC/LE---FFCD9703trialSurgeryChemo+SurgerypN111113R084%73%0.043yDFS25%40%5yDFS21%34%0.003HR0.65V.Boigeetal,ASCO2007abstr4510可切除胃癌圍手術(shù)期化療

5-FU+DDPinAGC/L24可切除胃癌圍手術(shù)期化療

Patientdata-basedmeta-analysis:CT+SvsS從12隨機(jī)試驗(yàn),2284患者中篩選出2102患者,涉及9個(gè)試驗(yàn),中位隨訪(fǎng)時(shí)間5.3年CT+SvsSHR0.87P=0.003轉(zhuǎn)化為5年絕對(duì)生存率提高4%R0切除率67%vs62%p=0.03P.G.Thirionetal,ASCO2007abstr4512可切除胃癌圍手術(shù)期化療

Patientdata-based25GAST-C1of2:preoperativechemoradiation2008.v.1NCCNguideline：

Paclitaxel/docetaxel+fluoropyrimidine(5-FUorcapecitabine)category2B；RecommendationofChineseversion:Docetaxelmightbechanged;Category2Bto3.Reason:StudyaboutPaclitaxel/5FU+RTisonlyphaseII.Noprospectivestudieshasbeensearchedondocetaxel/5-FU+RT(medline).？GAST-C1of2:preoperativech26Preoperativechemoradiation:phaseIIPhaseIITrialofPreoperativeChemoradiationinPatientsWithLocalizedGastricAdenocarcinoma(RTOG9904):QualityofCombinedModalityTherapyandPathologicResponse——JafferA.AjaniJCO2006：24（24）：3593Phase:IIPatients：43caseswithlocalizedGC(12%IB;37%II;52%III).，20centerMethods:2cysof5FU+CF+DDP——CRT(infusional5FU+weeklypaclitaxel)Resection（5to6weeksafterchemoradiotherapywascompleted.）Result：pathCR：26%R0resection：77%,1year：morepatientswithpathCR(82%)arelivingthanthosewithlessthanpathCR(69%）Preoperativechemoradiation:p27GAST-C1of2:preoperativechemoradiation2008.v.1NCCNguideline：

Paclitaxel/docetaxel+fluoropyrimidine(5-FU+capecitabine)category2B；RecommendationofChineseversion:Docetaxelmightbechanged;

Category2Bto3.GAST-C1of2:preoperativec282007.v.22008.v.1Postoperativechemo-therapyECFcategory1（onlywhenpreoperativeECFhasbeenadministered）ECFcategory1ECFmodificationcategory1（onlywhenpreoperativeECFhasbeenadministered）Postoperativechemo-radiationfluoropyrimidine/leucovorin1Fluoropyrimidine-based1Fluoropyrimidine/cisplatin2BECF2BTaxane-based2BFluoropyrimidine(5FUorcapecitabine)category1Updateof2008.v.1NCCNversionPostoperativechemotherapy?2007.v.22008.v.1Postoperative29StageIB-IV(M0)D0和D1占90%StageIB-IV(M0)30NCCN胃癌指南解讀講義課件31NCCN胃癌指南解讀講義課件32GAST-3:T3,T4oranyT,N1afterR0resection2008.v.1NCCNguideline：RT,45-50.4Gy+concurrent5-FUbasedradiosensitization(preferred)+5-FU±leucovorinorECFifreceivedpreoperatively（category1）RecommendationofChineseversion:AddfootnoteIfD0/D1resection:agreedtheabove;IfD2resection:postoperativechemotherapyrecommended.Evidence：D0/D1operationconsistsmorethan90%inINT0116；2MetaanalysisaboutadjuvantchemotherapyGASC-studyGAST-3:T3,T4oranyT,N1after33Patients:23trials，4919ptsMethods:Adjuvantchemotherapyarm(ArmA):2441Observationarm(ArmB):2478Results:3ySurvivalrate:60.6%inArmA,53.4%inArmB(RR:0.85,95%CI:0.80–0.90)DFS:ArmBhadashorterDFS(RR:0.88,95%CI:0.77–0.99)Recurrencerate:ArmAhadalowerrecurrencerate(RR:0.78,95%CI:0.710.86)Grade3/4ofAE(myelosuppressionandGI):morefrequentlyinArmA.Conclusion:Adjuvantchemotherapycouldimprovethesurvivalrateanddisease-freesurvivalrateingastriccanceraftercurativeresectionandreducetherelapserate.METAanalysisofAdjuvantchemotherapy1Anupdatedmeta-analysisofadjuvantchemotherapyaftercurativeresectionforgastriccancer——EuropeanJournalofSurgicalOncology(EJSO)

2008.02.002

Patients:23trials，4919ptsM34METAanalysisofAdjuvantchemotherapy2Theroleofpostoperativeadjuvantchemotherapyfollowingcurativeresectionforgastriccancer:ameta-analysisShu-LiangZhao;Jing-YuanFang.RenjiHospital,Shanghai,China.CancerInvestigation,May2008,Vol.26Issue3,p317-325,Patients:15trials，3212pts，Methods:Surgery+adjuvantchemotherapyvsSurgeryonlyResults:RRfordeathinthetreatedgroupwas0.90(P=0.0010).

Littleornosignificantbenefitsweresuggestedinsubgroupanalysesbetweendifferentpopulationandregimenseither.Conclusion:Postoperativeadjuvantchemotherapyforgastriccancerconfersslightlysignificantbenefitscomparedtothesurgeryonlygroup.

METAanalysisofAdjuvantchem35Postoperativeadjuvantchemotherapy——S1monotherapyAdjuvantchemotherapyforgastriccancerwithS-1,anoralfluoropyrimidine.——Sakuramoto,SNEnglJMed，2007，357：1810-1820

1004cases(stageII/III，D2,3yearsfollowup*S-1monotherapy529casesOS:80.5%OS:70.5%RandomizedphaseIIItrialcomparingS-1monotherapyversussurgeryaloneforstageII/IIIgastriccancerpatients(pts)aftercurativeD2gastrectomy(ACTS-GCstudy).2007Gastrointestinalcancersymposium,sasakoMSurgeryalone530cases*12/2005showedthatHRofdeathforS-1toCwas0.57,trialwasrecommendedtostop.09/2006HRofdeathforS-1was0.68.Conclusions:AdjuvantchemotherapywithS-1forgastriccancerisfeasibleandeffective.ThisregimencanbethestandardtreatmentforstageII/IIIgastriccancerptsaftercurativeD2dissection.ACTS-GCstudyJCOGPostoperativeadjuvantchemoth36PostoperativechemoradiationmightbeagoodoptiontocompensatetheinsufficiencyofthesurgerysuchasD0/D1resection.Adjuvantchemotherapyshowssurvivalbenefitcomparedwithsurgeryalone,especiallyafterD2resectionforpatientswithstageIIorhigher.Postoperativeadjuvantchemotherapy

Conclusion:Postoperativechemoradiationm37GAST-3：afterR1resection2008.v.1NCCNguideline：RT,45-50.4Gy+concurrent5-FU-basedradiosensitization(preferred)+5-FU±leucovorinRecommendationofChineseversion:

Toadd“Clinicaltrials”asanotheroption.Reason：R1resectionisnotradical,tillnow,nostandardtherapyhasbeenaccepted,itshouldbebettertofindtheappropriateonesbyclinicalstudies.GAST-3：afterR1resection2008.382007.v.22008.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof2008.v.1NCCNversionNoDDP+fluoropyrimidine(5-FUorcapecitabineorS－1)2BNopaclitaxel-basedregimens；2007.v.22008.v.1Metastaticor39V325研究結(jié)果TCF(多西紫杉醇、順鉑、5FU)是用于預(yù)后較好的患者的一項(xiàng)新的治療選擇Moiseyenkoetal,JCO2007,例數(shù)總體緩解疾病進(jìn)展時(shí)間（月）總生存期（月）3—4級(jí)毒性TCF221/22737%5.69.2腹瀉，感染，中性粒細(xì)胞減少癥*p=0.01p=0.0004p=0.02CF#4002224/23025%3.78.6胃炎，腎毒性*3－4級(jí)毒性包括：81％的非血液學(xué)毒性反應(yīng)，75％的血液學(xué)毒性反應(yīng)中30％伴有中性粒細(xì)胞減少性發(fā)熱V325研究結(jié)果TCF(多西紫杉醇、順鉑、5FU)是用于預(yù)40CPT-11forAGC——Ⅱ期多中心臨床研究

（2003ASCO）FFCD9803法國(guó)BoucheOetal.JClinOncol2004;22:4319–27例數(shù)RRmTTPmOSLV5FU24513%3.2m6.8mLV5FU2-DDP4427%4.9m9.5mLV5FU2-CPT-114540%6.7m11.3mCPT-11forAGC——Ⅱ期多中心臨床研究

（20041CPT-11聯(lián)合5-FU治療AGC

----III期臨床試驗(yàn)（2005ASCO）N=170CPT-1180mg/m2CF500mg/m25FU2000mg/m2civ1/Wx6wN=163CDDP100mg/m2d15FU1000mg/m2/dd1-5Q4WN=333AGCRR54（31.8%）42（25.8%）TTP5.0m4.2m(p=0.088)TTF4.0m3.4m(p=0.002)OS9.0m8.7mp＝0.53M.Dank2005ASCOabs4003CPT-11聯(lián)合5-FU治療AGC

----III期臨床試驗(yàn)42REAL-2:療效（Efficacy）EfficacyECF

N=263ECX

N=250EOF

N=245EOX

N=244P:ECFvsEOXRR(%)41464248

1yearOS(%)

37.740.840.446.8OS(mo)9.99.99.311.20.025Cunninghametal.ASCO2006LBA4017REAL-2:療效（Efficacy）EfficacyEC43ECFEOFECXEOXGrade3/4non-haematologicaltoxicity,%36423345Grade3/4neutropenia,%42305128p-value

0.0080.00430.001REAL2:安全性

safetyoutcomesECFEOFECXEOXGrade3/4non-haem44Oxaliplatin聯(lián)合EPI、5-FU/CF治療

晚期胃癌的臨床多中心研究——china用藥方法樂(lè)沙定100mg/m2d1EPI50mg/m2d1CF200mg/m2d1-35-FU500mg/m2CIVd1-3每3周重復(fù)，治療至少3個(gè)周期評(píng)價(jià)療效及毒性反應(yīng)CR2例（5.6%）PR13例（36.1%）SD17例（47.2%）

總有效率41.7%。其中初治患者9/20（45%）復(fù)治患者6/16（37.5%）]主要不良反應(yīng)：骨髓抑制：Ⅲ-ⅣOANC7/36（19.4%），ⅢOPLT3/36（8.3%），ⅢO

Hb4/36（11.1%），ⅢO神經(jīng)末梢毒性4/36（11.1%），以EPI為基礎(chǔ)的三藥聯(lián)合可行！EOX有明顯生存優(yōu)勢(shì)！Oxaliplatin聯(lián)合EPI、5-FU/CF治療

晚期胃45ML17032:CAPEvs5-FUinAGC

trialdesignFP

Cisplatin

80mg/m23-houri.v.infusion5-FUc.i.

800mg/m2/day;d1–5q3wXPCisplatin

80mg/m23-houri.v.infusionCapecitabine

1000mg/m2twicedaily;d1–14q3wKPS≥70%18–75yearsAdvancedand/or

metastaticgastriccancer(AGC)≥1measurablelesionNopriortreatmentforAGCR

A

N

D

OM

I

ZA

T

I

O

NML17032:CAPEvs5-FUinAGC

46SuperiorresponseratewithXPvs.FPConfirmedresponse

%(95%CI)XP

(n=160)FP

(n=156)p-valueOverallresponse41(33–49)29(22–37)0.030Completeresponse230.668Partialresponse39260.019Progressivedisease10180.041SuperiorresponseratewithXP47ML17032:XPvsFP

progression-freesurvival.HR0.81

EstimatedprobabilityHR=0.81(95%CI:0.63–1.04)ComparedtoHRupperlimit1.25,p=0.00080Months24681012141618202224261.00.80.60.40.20.0PerprotocolanalysisXP(n=139)FP(n=137)MedianPFS

months(95%CI)5.6(4.9–7.3)5.0(4.2–6.3)ML17032:XPvsFP

progression48相似的血液學(xué)不良發(fā)應(yīng)

XPvs.FP

%ofpatientsXP

(n=156)FP

(n=155)

Neutropenia3330Leukopenia1417Anemia125Thrombocytopenia66相似的血液學(xué)不良發(fā)應(yīng)

XPvs.FP

%ofpa49APhaseIITrialofCapecitabineplusDDPinAGC－－China2002.6-2003.5,N=145,Cape1000mg/m2Bidd1-14DDP20mg/m2ivd1-5q3W130ptsevaluable:98M/32FAge:53.7ysResultsCR10(8%)PR48(37%)SD51(39%)PD21(16%)OS12mSafety：grade3-4adverseevent<5%-----2005,2006ASCOAPhaseIITrialofCapecitabi50first-linechemotherapywithfluorouracil,leucovorinandoxaliplatin(FLO)versusfluorouracil,leucovorinandcisplatin(FLP)FLO

F2600mg/m224hinfusion,L200mg/m2,oxaliplatin85mg/m2q2wFLPF2000mg/m224hinfusion,qwL200mg/m2,qwcisplatin50mg/m2,q2w.Total220

ptsMedianage64yrs

Advancedand/or

metastaticgastriccancer(AGC)R

A

N

D

OM

I

ZA

T

I

O

NS.Al-Batran,J.Hartmann,ASCO2006TheprimaryendpointwasTTPfirst-linechemotherapywithf51SuperiorPerformancewithFLOvs.FLPConfirmedresponse

%(95%CI)FLO(N=98)FLP

(n=102)p-valueOverallresponse34%27%0.012TTP5.73.80.081TTF5.33.10.028S.Al-Batran,J.Hartmann,ASCO2006SuperiorPerformancewithFLO52PhaseIIStudyofS-1±DDPvs5-FU+DDPforGastricCancer(PI:MLJin)C:5-FU+DDPA:S-1B:S-1+DDPrandomizationAssumed180cases，60casesperarm，enrollmentcompletedObjective：RR,TTPPathologicallyconfirmed，unrectable，measurableleasionsEvidence：SC-101study

——2008ASCOmeetingPhaseIIStudyofS-1±DDPvs53ArmNCR+PRTTF(d)OS(d)N%A:S1771924.7*126★267＃B:S-1/CDDP742837.8159433C:5-FU/CDDP731419.2※85★309?！?ArmBcomparedwithArmC,P<0.05★:ArmBcomparedwithArmAandC,P<0.05＃:ArmBcomparedwithArmAandC,P<0.05*:ArmBcomparedwithArmA,P>0.05Evidence：SC-101study

——2008ASCOmeetingCR+PRN%A:S1771924.7*126★267＃54Elderlychemo-na?vepts(>=65years)withmeasurablemetastaticorrecurrentgastriccancerarmX(N=46,Medianage=71.0years

)Capecitabine(1,250mg/m2bid,D1-14every3weeks)

armS(N=45,Medianage=70.5years)S-1(40~60mgbidD1-28every6weeks)

randomly10/2004-4/2006

Arandomizedmulti-centerphaseIItrial：

capecitabine(X)versusS-1(S)asfirst-linetreatment

inelderlypatientswithmAGCY.Kang,D.Shin

2007ASCOAnnualMeetingElderlychemo-na?vepts(>=6555Arandomizedstudy:theactivityandsafetyofcapecitabinevsS-1inelderlyptswithAGCphaseII

Y.Kang,

JCO,2007ASCOMeetingsProceedingsPartI.Vol25,No.18S:4546)

Evidence：capecitabinevsS-1

PhaseIIXeloda(n=44)S-1(n=45)Regimen1250mg/㎡bidd1-14/3W40-60mg/㎡bidd1-28/6WCR(%)01(2.2%)PR(%)13(29.5)12(26.7)mOS(mo)10.07.9mTTP(mo)4.84.2mTTF(mo)4.43Arandomizedstudy:theactivi56Xeloda(n=44)S-1(n=45)Grade3/4(%)1250mg/㎡bidd1-14/3W40-60mg/㎡bidd1-28/6WLeukopenia6.84.8Asthenia07.2Anorexia6.89.5Diarrhea2.30HFS6.80Evidence：capecitabinevsS-1toxityXeloda(n=44)S-1(n=45)Grade572007.v.22008.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof2008.v.1NCCNversionDDP+fluoropyrimidine(5-FUorcapecitabineorS－1)2B2007.v.22008.v.1Metastaticor58arandomizedphaseIItrialoftheSwissGroupforClinicalCancerResearch.Chemotherapy-naivepatientsECFvsDCvsDCFEvidence1:docetaxel——RothAD,FazioN,etal,JClinOncol.2007Aug1;25(22):3217-23.n=119ECFDCDCFORR25.0%18.5%36.6%MedianOS8.311.010.4neutropeniaG3/434%49%57%QOLsimilararandomizedphaseIItrialof59arandomizedphaseIIstudyinGermanypatientswithuntreated,advancedgastricadenocarcinoma.Evidence2:docetaxel——Thuss-PatiencePC,KretzschmarA,etal：JClinOncol.2005Jan20;23(3):494-501.

n=90ECFDFORR35.6%37.8%MedianOS9.7m9.5mTTP5.3m5.5marandomizedphaseIIstudyin60arandomizedphaseIItrial106patientsincludedwDCFvswDXwDCF

:DOC

30mg/m2d1d8;DDP60mg/m2;5-Fu200mg/m2civwDX

DOC

30mg/m2d1d8;

CAPE1600mg/m2d1-14Evidence3:docetaxel（Weekly）——N.Tebbutt,etal,Asco2007,4528.

wDCFn=50wDXn=56CR+PR%4926Febrileneutropenia%42Gr?lethargy%104Gr?diarrhea%107Gr?stomatitis%222Gr3hand-footSyn%42OSmonths12.810.1arandomizedphaseIItrialEvi61Evidence:paclitaxelvsdocetaxelPaclitaxelversusdocetaxelforadvancedgastriccancer:arandomizedphaseIItrialincombinationwithinfusional5-fluorouracil.

——ParkSHetal,AnticancerDrugs.2006Feb;17(2):225-9Phase:II,randomizedPatients：77caseswithmeasurablemetastaticgastriccancer(PFvsDF).Methods:

PXL+5-FuvsDOC+5-FuResult：responserate(42vs33%,P=0.53)overallsurvival(9.9vs9.3m;P=0.42)grade3/4toxicities(68vs85%;P=0.09)Globalqualityoflife:similarpain,dyspnea,constipationanddiarrheafavoredPFConclusion:

BothPFandDFappeartohaveefficacyagainstmetastaticgastriccancer,withdifferent,butacceptable,safetyprofiles.Evidence:paclitaxelvsdocet622007.v.22008.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof2008.v.1NCCNversionDCFmodification：PF/DF/wDCF/DC/DX/PXshouldbeadded2007.v.22008.v.1Metastaticor632008.v.1NCCNguideline:RecommendationofChineseversion:Toaddcisplatinplusfluoropyrimidine(5-FUorcapecitabine)category2BToaddfluoropyrimidine(5-FUorcapecitabine)foroldpatientsorpoorperformancestatus.Category2BGAST-C1of2:

metastaticorlocallyadvancedcancer2008.v.1NCCNguideline:GAST-C64GAST-C1of2:preoperativechemoradiation

Docetaxelmightbechanged;Category2Bto3.GAST-3:T3,T4oranyT,N1afterR0resection

Addfootnote:IfD0/D1resection:agreedtheabove(CT+RT);IfD2resection:postoperativechemotherapyrecommended.GAST-C1of2:postoperativechemotherapyToaddS-1(category2B)withfootnote(notavailabeinmarketnow)GAST-3：afterR1resectionToadd“Clinicaltrials”asanotheroption.GAST-C1of2:metastaticorlocallyadvancedcancerDCFmodification：PF/DF/wDCF/DC/DX/PXshouldbeaddedcategory2BToaddcisplatinplusfluoropyrimidine(5-FUorcapecitabine)category2BToaddfluoropyrimidine(5-FUorcapecitabine)foroldpatientsorpoorperformancestatus.Category2BRecommendationofChineseversion:GAST-C1of2:preoperativech65概念的更新：在整個(gè)治療指南中將chemotherapy/RT更改為chemoradiation，salvage改為palliative強(qiáng)調(diào)多學(xué)科協(xié)作在胃癌綜合治療中的重要地位，要求多學(xué)科會(huì)議討論患者所有三個(gè)治療途徑的抉擇，并增加綜合治療模式原則新頁(yè)細(xì)化、更新手術(shù)、化療、放療原則術(shù)前分期檢查PET－CT或EUS的應(yīng)用強(qiáng)調(diào)術(shù)前新輔助化療或放化療的地位：T2以上分期患者將術(shù)前化療作為一類(lèi)推薦首選治療手段。followup：近端胃大部或全胃切除者，應(yīng)監(jiān)測(cè)并補(bǔ)充VitB12NCCN胃癌臨床指南v.1.2008重要更新NCCNClinicalPrecticeguidelinesinOncologyChineseversion1.2008----GastricCancer概念的更新：在整個(gè)治療指南中將chemotherapy/RT66NCCN胃癌臨床指南中國(guó)版

與NCCN達(dá)成幾點(diǎn)共識(shí)手術(shù)根治性切除:D2，切緣≥5cmN分期聯(lián)合美國(guó)及日本標(biāo)準(zhǔn)（兩份分期標(biāo)準(zhǔn)共同附上）病理檢查報(bào)告要求規(guī)范（另附1頁(yè)）在綜述中說(shuō)明放療條件和要求→新增放療原則新頁(yè)術(shù)前放化療問(wèn)題術(shù)后輔助化療問(wèn)題晚期胃癌姑息治療，化療方案的選擇以及循證醫(yī)學(xué)證據(jù)等級(jí)NCCNClinicalPrecticeguidelinesinOncologyChineseversion1.2008----GastricCancerNCCN胃癌臨床指南中國(guó)版

與NCCN達(dá)成幾點(diǎn)共識(shí)手術(shù)根治性67今后需要探討的問(wèn)題和發(fā)展趨勢(shì)術(shù)前化療或放化療的意義和實(shí)施規(guī)范手術(shù)根治術(shù)后的輔助化療放化療的聯(lián)合在輔助及姑息治療中的作用全身化療藥物、方案的優(yōu)化、組合靶向藥物在胃癌治療中的作用NCCNClinicalPrecticeguidelinesinOncologyChineseversion1.2007