NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座

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)科沈琳腫瘤學(xué)臨床實(shí)踐指南（中國(guó)版）年第一版胃癌NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第1頁(yè)Copyright?AmericanCancerSocietyAge-standardizedIncidenceRatesforStomachCancerinworld.FromParkin,D.M.etal.CACancerJClin;55:74-108.世界胃癌年紀(jì)調(diào)整發(fā)病率NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第2頁(yè)對(duì)1990-1992年中國(guó)1/10萬人口死因抽樣調(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（M：32.8/10萬，F(xiàn)：17.0/10萬），占全部惡性腫瘤死亡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，女性：18.6/10萬，分別是歐美發(fā)達(dá)國(guó)家4.2-7.9倍，3.8-8.0倍有顯著地域差異和城鎮(zhèn)差異。全國(guó)抽樣調(diào)查263個(gè)點(diǎn)，胃癌調(diào)整死亡率在2.5-153.0/10萬之間，Urbanareas:15.3/10萬;Ruralareas:24.4/10萬，是城市1.6倍NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第3頁(yè)NCCN共識(shí)分類1類：基于高水平證據(jù)，NCCN達(dá)成共識(shí)，推薦應(yīng)用2A類：基于包含臨床經(jīng)驗(yàn)在內(nèi)稍低水平證據(jù)，NCCN達(dá)成共識(shí)，推薦應(yīng)用。2B類：基于包含臨床經(jīng)驗(yàn)在內(nèi)稍低水平證據(jù)，NCCN未達(dá)成統(tǒng)一共識(shí)（但無較大分歧）。3類：NCCN對(duì)該提議適宜性存在較大分歧。除非尤其說明，本指南中全部提議均達(dá)成2A類共識(shí)。NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第4頁(yè)NCCN胃癌臨床實(shí)踐指南

第1版指南更新主要改變總結(jié)（GAST-1）：workup：PET/CT掃描和EUS作為可選檢驗(yàn)項(xiàng)目。（GAST－2）：要求多學(xué)科會(huì)議討論患者全部三個(gè)治療路徑抉擇T2以上分期患者將術(shù)前化療作為一類推薦首選治療伎倆。術(shù)前放化療作為2B類首選治療伎倆。（GAST－3）：R0術(shù)后分期T2N0M0及以上者，如術(shù)前采取ECF方案化療，術(shù)后可選擇ECF繼續(xù)（1類）（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）：增加綜合治療模式標(biāo)準(zhǔn)新頁(yè)（GAST－B、C）：更新外科及系統(tǒng)化療標(biāo)準(zhǔn)（GAST－A）：新增放療標(biāo)準(zhǔn)新頁(yè)NCCNguidelines----GastricCancerChineseversion1.在整個(gè)治療指南中將chemotherapy/RT更改為chemoradiation將salvage改為palliativeNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第5頁(yè)與版類似注意：除了尤其指出情況，全部推薦治療都是2A證據(jù)。臨床試驗(yàn)：NCCN認(rèn)為對(duì)于任何一個(gè)腫瘤病人參加臨床試驗(yàn)都取得最正確治療.要尤其勉勵(lì)參加臨床試驗(yàn)。NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第6頁(yè)強(qiáng)調(diào)多學(xué)科評(píng)定和協(xié)作！NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第7頁(yè)多學(xué)科綜合治療模式有益于局部進(jìn)展期胃癌患者（1類證據(jù)）NCCN教授組基本觀點(diǎn)：不勉勵(lì)單一學(xué)科組員單方面進(jìn)行治療決議。具備以下條件，可能給局部進(jìn)展期胃癌患者以最正確綜合治療：例會(huì)形勢(shì)實(shí)用（一周或2周一次），相關(guān)學(xué)科機(jī)構(gòu)和個(gè)人定時(shí)來共同回顧患者詳細(xì)資料。每次例會(huì)，各相關(guān)學(xué)科都要主動(dòng)參加，包含腫瘤外科，腫瘤內(nèi)科，消化科，放射科，病理科。另外，最好還能包含營(yíng)養(yǎng)科，社工，護(hù)理以及其它支持學(xué)科。全部長(zhǎng)久治療策略要在全方面分期檢驗(yàn)完成后再進(jìn)行，最好在全部治療開始之前。決議前共同回顧原始醫(yī)學(xué)數(shù)據(jù)而非單純閱讀匯報(bào)。多學(xué)科團(tuán)體做出共識(shí)推薦并摘要統(tǒng)計(jì)在案，對(duì)每位患者是有益。特定患者主要治療小組或醫(yī)生應(yīng)尊重以及考慮多學(xué)科團(tuán)體所做出共識(shí)推薦。反饋部分患者治療隨訪結(jié)果，對(duì)整個(gè)多學(xué)科團(tuán)體是有效實(shí)例教育方式。在例會(huì)期間，正式定時(shí)復(fù)習(xí)相關(guān)文件，對(duì)整個(gè)多學(xué)科團(tuán)體是高效教育方式。NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第8頁(yè)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第9頁(yè)分期CT掃描±EUS判斷病灶范圍腹腔鏡有利于部分患者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(包含腹腔脫落細(xì)胞學(xué)陽性可切除腫瘤T1者在有經(jīng)驗(yàn)者可采取內(nèi)鏡下胃粘膜切除T1-T3適當(dāng)腫瘤切緣≥4cm（5cm）,鏡下陰性推薦D1/D2淋巴結(jié)清掃,應(yīng)最少檢驗(yàn)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受侵可考慮留置空腸營(yíng)養(yǎng)管姑息手術(shù)能夠接收切緣陽性，淋巴結(jié)不強(qiáng)求清掃胃腸短路或營(yíng)養(yǎng)管外科治療標(biāo)準(zhǔn)NCCNv.1.GastricCancerNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第10頁(yè)結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第11頁(yè)JapaneseGastriccancerassociati（JGCA)腹腔細(xì)胞學(xué)（CY）CY0腹腔細(xì)胞學(xué)良性或無法確定CY1腹腔細(xì)胞學(xué)未見癌細(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ST-3）淋巴結(jié)轉(zhuǎn)移程度N0無淋巴結(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)無轉(zhuǎn)移N2第二站淋巴結(jié)有轉(zhuǎn)移，第三站淋巴結(jié)無轉(zhuǎn)移N3第三站淋巴結(jié)有轉(zhuǎn)移Nx區(qū)域淋巴結(jié)無法評(píng)定肝轉(zhuǎn)移（H）H0無肝轉(zhuǎn)移H1有肝轉(zhuǎn)移Hx不清楚腹膜轉(zhuǎn)移（P）P0無腹膜轉(zhuǎn)移P1有腹膜轉(zhuǎn)移*本分期源自JapaneseGastricCancerAssociation.JapaneseClassificationofGastricCarcinoma-2ndEnglishEdition.GastricCancer(1998)1:10–24?腫瘤能夠穿透固有肌層達(dá)胃結(jié)腸韌帶或肝胃韌帶或大小網(wǎng)膜，但沒有穿透這些結(jié)構(gòu)臟層腹膜。在這種情況下，原發(fā)腫瘤分期為T2。假如穿透覆蓋胃韌帶或網(wǎng)膜臟層腹膜，則應(yīng)該被分為T3期。?腫瘤侵犯大、小網(wǎng)膜、食管和十二指腸不作為T4,經(jīng)胃壁內(nèi)擴(kuò)展至十二指腸或食管腫瘤分期取決于包含胃在內(nèi)這些部位最大浸潤(rùn)深度?！霱1種類應(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,M1NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第12頁(yè)RegionalLNGroupAccordingtoLocationofTumorD14d4d4d653D211p12a14v1998a97LD/LNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第13頁(yè)Sasakoetal: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.JClinOncol.24(18S):LBA4015.擴(kuò)大根治orD2?——循證醫(yī)學(xué)證據(jù)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第14頁(yè)AprospectiverandomizedcontrolledclinicaltrialinTaiwan:D2vsD15-yearsurvivalD2dissectionwassuperiortoD1dissection

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

WuCW,HsiungCA,LoSS,etal.Nodaldissectionforpatientswithgastriccancer:Arandomizedcontrolledtrial.LancetOncol;7:309-315深入臨床試驗(yàn)，尤其是觀察手術(shù)前后輔助治療應(yīng)該基于D2式手術(shù)！D1orD2?——循證醫(yī)學(xué)證據(jù)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第15頁(yè)適合于全部胃癌胃切除標(biāo)本原發(fā)性胃癌胃切除標(biāo)本檢驗(yàn)原發(fā)性腫瘤*外科切緣評(píng)定?淋巴結(jié)評(píng)定?原發(fā)性胃癌組織學(xué)類型§Lauren分類，1965日本胃癌研究協(xié)會(huì)（JRSGC）分類，1981WHO分類，病理學(xué)分期（pTNM）應(yīng)包含以下參數(shù)：腫瘤惡性程度（分級(jí)）ξ浸潤(rùn)深度淋巴結(jié)部位、數(shù)目及陽性數(shù)遠(yuǎn)端及近端外科切緣情況注釋胃癌原發(fā)腫瘤檢驗(yàn)應(yīng)包含：腫瘤在胃粘膜確切位置及腫瘤范圍；腫瘤距近端和遠(yuǎn)端外科切緣距離；腫瘤大致形態(tài)，包含腫瘤大小、早期胃癌形態(tài)類型；腫瘤切面，浸潤(rùn)胃壁情況。?外科切緣評(píng)定：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：外科切緣潔凈；R1：外科切緣鏡下陽性；R2：外科切緣肉眼陽性。提議切除近端切緣應(yīng)距腫瘤邊緣5cm，同時(shí)應(yīng)常規(guī)術(shù)中切緣冰凍檢驗(yàn)。?淋巴結(jié)評(píng)定：見ST-1/2/3。依據(jù)胃切除時(shí)淋巴結(jié)清掃范圍分為：D0：淋巴結(jié)清掃范圍不包含全部N1淋巴結(jié)；D1：淋巴結(jié)清掃范圍不包含全部N2淋巴結(jié)；D2：淋巴結(jié)清掃范圍不包含全部N3淋巴結(jié)。按照AJCC標(biāo)準(zhǔn)，因?yàn)楸粰z驗(yàn)淋巴結(jié)數(shù)量和淋巴結(jié)陽性率之間有正相關(guān)，應(yīng)檢驗(yàn)最少15個(gè)淋巴結(jié)。§胃癌組織學(xué)類型Lanren分類（1965）：腸型；彌漫型JRSGC分類（1981）：乳頭狀型管狀型低分化型 粘液型印戒細(xì)胞型WHO分類（）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%。提議使用AJCC/UICC分類，在病理匯報(bào)中N分期可增加標(biāo)注JRSGC要求淋巴結(jié)部位。病理診療標(biāo)準(zhǔn)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第16頁(yè)系統(tǒng)化療標(biāo)準(zhǔn)NEW遵照原始文件報(bào)道藥品劑量/方案,合理用藥并進(jìn)行適當(dāng)調(diào)整患者適當(dāng)器官功效和體力情況充分考慮化療毒性和益處,并一直與患者及家眷討論/交流,并進(jìn)行患者教育,警示并防治不良反應(yīng),防止嚴(yán)重合并癥及縮短連續(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)定療效和長(zhǎng)久合并癥NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第17頁(yè).v.2.v.1Preoperativechemo-therapyECFcategory1ECFcategory1ECFmodificationcategory1Preoperativechemo-radiationfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BTaxanes-based2BIrinotecan-based2Bpaclitaxel/Docetaxel+fluoropyrimidine(5FU/capecitabine）category2BUpdateof.v.1NCCNversionNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第18頁(yè)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.CuuninghamASCOabs4001Cunninghametal,NEJMNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第19頁(yè)Chemo+SurgerySurgeryPatients250253Age6262ToSurgery219(88%)240(95%)PtswithR0resection169(68%)*166(66%)*Nopathologiccompleteresponses可切除胃癌圍手術(shù)期化療

---MAGICtrialCunninghametal,NEJMNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第20頁(yè)Chemo+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,NEJM可切除胃癌圍手術(shù)期化療

---MAGICtrialNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第21頁(yè)OverallSurvivalPatientsatriskLogrankp-value=0.009HazardRatio=0.75

(95%CI0.60-0.93)CSCS250168111795238272531558050311890.00.10.20.30.40.50.60.70.80.91.0Monthsfromrandomization0122436486072149250170253EventsTotalCSCSSurvivalrateNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第22頁(yè)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5.7Y賁門、胃89％食管11％NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第23頁(yè)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,ASCOabstr4510NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第24頁(yè)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,包括9個(gè)試驗(yàn),中位隨訪時(shí)間5.3年CT+SvsSHR0.87P=0.003轉(zhuǎn)化為5年絕對(duì)生存率提升4%R0切除率67%vs62%p=0.03P.G.Thirionetal,ASCOabstr4512NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第25頁(yè)GAST-C1of2:preoperativechemoradiation.v.1NCCNguideline：

Paclitaxel/docetaxel+fluoropyrimidine(5-FUorcapecitabine)category2B；RecommendationofChineseversion:Docetaxelmightbechanged;Category2Bto3.Reason:StudyaboutPaclitaxel/5FU+RTisonlyphaseII.Noprospectivestudieshasbeensearchedondocetaxel/5-FU+RT(medline).？NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第26頁(yè)P(yáng)reoperativechemoradiation:phaseIIPhaseIITrialofPreoperativeChemoradiationinPatientsWithLocalizedGastricAdenocarcinoma(RTOG9904):QualityofCombinedModalityTherapyandPathologicResponse——JafferA.AjaniJCO：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%）NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第27頁(yè)GAST-C1of2:preoperativechemoradiation.v.1NCCNguideline：

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

Category2Bto3.NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第28頁(yè).v.2.v.1Postoperativechemo-therapyECFcategory1（onlywhenpreoperativeECFhasbeenadministered）ECFcategory1ECFmodificationcategory1（onlywhenpreoperativeECFhasbeenadministered）Postoperativechemo-radiationfluoropyrimidine/leucovorin1Fluoropyrimidine-based1Fluoropyrimidine/cisplatin2BECF2BTaxane-based2BFluoropyrimidine(5FUorcapecitabine)category1Updateof.v.1NCCNversionPostoperativechemotherapy?NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第29頁(yè)StageIB-IV(M0)D0和D1占90%NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第30頁(yè)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第31頁(yè)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第32頁(yè)GAST-3:T3,T4oranyT,N1afterR0resection.v.1NCCNguideline：RT,45-50.4Gy+concurrent5-FUbasedradiosensitization(preferred)+5-FU±leucovorinorECFifreceivedpreoperatively（category1）RecommendationofChineseversion:AddfootnoteIfD0/D1resection:agreedtheabove;IfD2resection:postoperativechemotherapyrecommended.Evidence：D0/D1operationconsistsmorethan90%inINT0116；2MetaanalysisaboutadjuvantchemotherapyGASC-studyNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第33頁(yè)P(yáng)atients: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)

.02.002

NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第34頁(yè)METAanalysisofAdjuvantchemotherapy2Theroleofpostoperativeadjuvantchemotherapyfollowingcurativeresectionforgastriccancer:ameta-analysisShu-LiangZhao;Jing-YuanFang.RenjiHospital,Shanghai,China.CancerInvestigation,May,Vol.26Issue3,p317-325,Patients:15trials，3212pts，Methods:Surgery+adjuvantchemotherapyvsSurgeryonlyResults:RRfordeathinthetreatedgroupwas0.90(P=0.0010).

Littleornosignificantbenefitsweresuggestedinsubgroupanalysesbetweendifferentpopulationandregimenseither.Conclusion:Postoperativeadjuvantchemotherapyforgastriccancerconfersslightlysignificantbenefitscomparedtothesurgeryonlygroup.

NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第35頁(yè)P(yáng)ostoperativeadjuvantchemotherapy——S1monotherapyAdjuvantchemotherapyforgastriccancerwithS-1,anoralfluoropyrimidine.——Sakuramoto,SNEnglJMed，，357：1810-1820

1004cases(stageII/III，D2,3yearsfollowup*S-1monotherapy529casesOS:80.5%OS:70.5%RandomizedphaseIIItrialcomparingS-1monotherapyversussurgeryaloneforstageII/IIIgastriccancerpatients(pts)aftercurativeD2gastrectomy(ACTS-GCstudy).Gastrointestinalcancersymposium,sasakoMSurgeryalone530cases*12/showedthatHRofdeathforS-1toCwas0.57,trialwasrecommendedtostop.09/HRofdeathforS-1was0.68.Conclusions:AdjuvantchemotherapywithS-1forgastriccancerisfeasibleandeffective.ThisregimencanbethestandardtreatmentforstageII/IIIgastriccancerptsaftercurativeD2dissection.ACTS-GCstudyJCOGNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第36頁(yè)P(yáng)ostoperativechemoradiationmightbeagoodoptiontocompensatetheinsufficiencyofthesurgerysuchasD0/D1resection.Adjuvantchemotherapyshowssurvivalbenefitcomparedwithsurgeryalone,especiallyafterD2resectionforpatientswithstageIIorhigher.Postoperativeadjuvantchemotherapy

Conclusion:NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第37頁(yè)GAST-3：afterR1resection.v.1NCCNguideline：RT,45-50.4Gy+concurrent5-FU-basedradiosensitization(preferred)+5-FU±leucovorinRecommendationofChineseversion:

Toadd“Clinicaltrials”asanotheroption.Reason：R1resectionisnotradical,tillnow,nostandardtherapyhasbeenaccepted,itshouldbebettertofindtheappropriateonesbyclinicalstudies.NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第38頁(yè).v.2.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof.v.1NCCNversionNoDDP+fluoropyrimidine(5-FUorcapecitabineorS－1)2BNopaclitaxel-basedregimens；NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第39頁(yè)V325研究結(jié)果TCF(多西紫杉醇、順鉑、5FU)是用于預(yù)后很好患者一項(xiàng)新治療選擇Moiseyenkoetal,JCO,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)胞降低癥*p=0.01p=0.0004p=0.02CF#4002224/23025%3.78.6胃炎，腎毒性*3－4級(jí)毒性包含：81％非血液學(xué)毒性反應(yīng)，75％血液學(xué)毒性反應(yīng)中30％伴有中性粒細(xì)胞降低性發(fā)燒NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第40頁(yè)CPT-11forAGC——Ⅱ期多中心臨床研究

（ASCO）FFCD9803法國(guó)BoucheOetal.JClinOncol;22:4319–27例數(shù)RRmTTPmOSLV5FU24513%3.2m6.8mLV5FU2-DDP4427%4.9m9.5mLV5FU2-CPT-114540%6.7m11.3mNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第41頁(yè)CPT-11聯(lián)合5-FU治療AGC

----III期臨床試驗(yàn)（ASCO）N=170CPT-1180mg/m2CF500mg/m25FUmg/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.DankASCOabs4003NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第42頁(yè)REAL-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.ASCOLBA4017NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第43頁(yè)ECFEOFECXEOXGrade3/4non-haematologicaltoxicity,%36423345Grade3/4neutropenia,%42305128p-value

0.0080.00430.001REAL2:安全性

safetyoutcomesNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第44頁(yè)Oxaliplatin聯(lián)合EPI、5-FU/CF治療

晚期胃癌臨床多中心研究——china用藥方法樂沙定100mg/m2d1EPI50mg/m2d1CF200mg/m2d1-35-FU500mg/m2CIVd1-3每3周重復(fù)，治療最少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)三藥聯(lián)合可行！EOX有顯著生存優(yōu)勢(shì)！NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第45頁(yè)ML17032: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

NNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第46頁(yè)SuperiorresponseratewithXPvs.FPConfirmedresponse

%(95%CI)XP

(n=160)FP

(n=156)p-valueOverallresponse41(33–49)29(22–37)0.030Completeresponse230.668Partialresponse39260.019Progressivedisease10180.041NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第47頁(yè)ML17032: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)NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第48頁(yè)相同血液學(xué)不良發(fā)應(yīng)

XPvs.FP

%ofpatientsXP

(n=156)FP

(n=155)

Neutropenia3330Leukopenia1417Anemia125Thrombocytopenia66NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第49頁(yè)APhaseIITrialofCapecitabineplusDDPinAGC－－China.6-.5,N=145,Cape1000mg/m2Bidd1-14DDP20mg/m2ivd1-5q3W130ptsevaluable:98M/32FAge:53.7ysResultsCR10(8%)PR48(37%)SD51(39%)PD21(16%)OS12mSafety：grade3-4adverseevent<5%-----,ASCONCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第50頁(yè)first-linechemotherapywithfluorouracil,leucovorinandoxaliplatin(FLO)versusfluorouracil,leucovorinandcisplatin(FLP)FLO

F2600mg/m224hinfusion,L200mg/m2,oxaliplatin85mg/m2q2wFLPFmg/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,ASCOTheprimaryendpointwasTTPNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第51頁(yè)SuperiorPerformancewithFLOvs.FLPConfirmedresponse

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

(n=102)p-valueOverallresponse34%27%0.012TTP5.73.80.081TTF5.33.10.028S.Al-Batran,J.Hartmann,ASCONCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第52頁(yè)P(yáng)haseIIStudyofS-1±DDPvs5-FU+DDPforGastricCancer(PI:MLJin)C:5-FU+DDPA:S-1B:S-1+DDPrandomizationAssumed180cases，60casesperarm，enrollmentcompletedObjective：RR,TTPPathologicallyconfirmed，unrectable，measurableleasionsEvidence：SC-101study

——ASCOmeetingNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第53頁(yè)ArmNCR+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

——ASCOmeetingNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第54頁(yè)Elderlychemo-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/-4/

Arandomizedmulti-centerphaseIItrial：

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

inelderlypatientswithmAGCY.Kang,D.Shin

ASCOAnnualMeetingNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第55頁(yè)Arandomizedstudy:theactivityandsafetyofcapecitabinevsS-1inelderlyptswithAGCphaseII

Y.Kang,

JCO,ASCOMeetingsProceedingsPartI.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)4.43NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第56頁(yè)Xeloda(n=44)S-1(n=45)Grade3/4(%)1250mg/㎡bidd1-14/3W40-60mg/㎡bidd1-28/6WLeukopenia6.84.8Asthenia07.2Anorexia6.89.5Diarrhea2.30HFS6.80Evidence：capecitabinevsS-1toxityNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第57頁(yè).v.2.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof.v.1NCCNversionDDP+fluoropyrimidine(5-FUorcapecitabineorS－1)2BNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第58頁(yè)arandomizedphaseIItrialoftheSwissGroupforClinicalCancerResearch.Chemotherapy-naivepatientsECFvsDCvsDCFEvidence1:docetaxel——RothAD,FazioN,etal,JClinOncol.Aug1;25(22):3217-23.n=119ECFDCDCFORR25.0%18.5%36.6%MedianOS8.311.010.4neutropeniaG3/434%49%57%QOLsimilarNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第59頁(yè)arandomizedphaseIIstudyinGermanypatientswithuntreated,advancedgastricadenocarcinoma.Evidence2:docetaxel——Thuss-PatiencePC,KretzschmarA,etal：JClinOncol.Jan20;23(3):494-501.

n=90ECFDFORR35.6%37.8%MedianOS9.7m9.5mTTP5.3m5.5mNCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第60頁(yè)arandomizedphaseIItrial106patientsincludedwDCFvswDXwDCF

:DOC

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

DOC

30mg/m2d1d8;

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

wDCFn=50wDXn=56CR+PR%4926Febrileneutropenia%42Gr?lethargy%104Gr?diarrhea%107Gr?stomatitis%222Gr3hand-footSyn%42OSmonths12.810.1NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第61頁(yè)Evidence:paclitaxelvsdocetaxelPaclitaxelversusdocetaxelforadvancedgastriccancer:arandomizedphaseIItrialincombinationwithinfusional5-fluorouracil.

——ParkSHetal,AnticancerDrugs.Feb;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.NCCN胃癌臨床實(shí)踐指南中國(guó)版解讀專家講座第62頁(yè).v.2.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF