1、从规范化资料解读看胃癌综合治疗AJCC 分期 7th edition ，2010，10UICCNCCN指南， 2011，3NCCN 美国国家癌症综合网络ESMO指南，2010，8ESMO 欧洲临床肿瘤学会卫生部胃癌诊疗规范， 2011，3卫生部医政司牵头，国内30余位专家参与（外科、内科、放射诊断、放射治疗、病理等）制定了胃腺癌，包括胃食管结合部癌的诊断、治疗和随访原则，适用于具备相应资质的卫生机构及其医务人员对胃癌的诊断和治疗卫生部胃癌诊疗规卫生部胃癌诊疗规范范NCCNESMOl必须必须l建议建议l酌情使用酌情使用/考虑考虑l不推荐不推荐推荐级别来自推荐级别来自ASCO标准：标准：l 1类：
2、类： 基于高水平证据基于高水平证据(如随机如随机对照试验对照试验)提出的建议，专家组提出的建议，专家组一致同意。一致同意。l 2A类：基于低水平证据提出的类：基于低水平证据提出的建议，专家组一致同意。建议，专家组一致同意。l 2B类：基于低水平证据提出的类：基于低水平证据提出的建议，专家组基本同意，无明显建议，专家组基本同意，无明显分歧。分歧。l 3类：类： 基于任何水平证据提出基于任何水平证据提出的建议，专家组意见存在明显的的建议，专家组意见存在明显的分歧。分歧。除非特别之处，除非特别之处，NCCN对所有建对所有建议均达成议均达成2A类共识。类共识。推荐级别和推荐级别和NCCN一致，一致，为
3、为ASCO标准标准另注明证据级别：另注明证据级别：l I：所有：所有RCT的系统评价或的系统评价或Meta分析；分析；l II：单个的大样本：单个的大样本 RCTl III：有对照但未随机：有对照但未随机 Traill IV：无对照的系列病例观察：无对照的系列病例观察无特别注明级别之描述，是无特别注明级别之描述，是ESMO专家认为的临床标准专家认为的临床标准治疗原则诊断与分期早期胃癌，手术及相关系统化疗总则围手术期化疗姑息化疗一线二线化疗ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范应采取综合治疗的原则，即根据肿瘤病理学类型及临床分期，结合患者一般状况和器官功能状态，以手术、化疗、放疗乃至生物
4、靶向治疗等多学科综合治疗模式（multidisciplinary team，MDT），有计划地、合理地应用治疗手段，以期达到：根治或最大幅度地控制肿瘤延长患者生存期改善生活质量ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范近年来胃癌治疗最大的进展是通过胃癌围手术期治疗和辅助放化疗的综合治疗模式明显改善患者的生存期NCCN 指南结合外科、化疗和放疗医生，消化、影像和病理科的多学科综合治疗是必不可少的ESMO（欧洲临床肿瘤学会）临床诊断、治疗和随访指南 胃癌治疗应是以手术治疗为主的综合治疗胃癌治疗应是以手术治疗为主的综合治疗胃癌诊疗推荐流程胃癌诊疗推荐流程ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗
5、规范分类标准：WHO胃癌组织学分类分期诊断标准：AJCC TNM分期标准（2010年）病理学描述：另有附录ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范卫生部胃癌诊疗规范采用以下标准：卫生部胃癌诊疗规范采用以下标准：胃镜检查：确诊胃癌的必须检查手段，可确定肿瘤位置，同时获得组织标本以行病理检查；可酌情选用色素内镜或放大内镜检查超声胃镜检查：推荐用于胃癌的术前分期，有助于评价胃癌浸润深度和判断胃周淋巴结转移状况。对拟施行内镜粘膜切除（EMR）、内镜粘膜下层切除（ESD）者等微创手术者则为必须腹腔镜：对怀疑腹膜转移或腹腔内播散者，可考虑腹腔镜检查ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范组织病
6、理学诊断是胃癌的确诊和治疗依据。活检确诊为浸润性癌的病例进行规范化治疗如因活检取材的限制，活检病理不能确定浸润深度。报告为癌前病变或可疑浸润的病例，建议临床医师重复活检或结合影像学检查情况，进一步确诊后选择治疗方案ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范CT： 应作为胃癌术前分期的常规方法。在无造影剂使用禁忌症情况下，建议在胃腔呈良好充盈状态下进行增强CT扫描。扫描部位应包括原发部位及可能的转移部位磁共振（MRI）检查：是重要的补充手段。推荐以下情况选用：对CT造影剂过敏者其它影像学检查怀疑转移者，如肝转移、卵巢转移等MRI有助于判断腹膜转移状态，可酌情使用ref：卫生部胃癌诊疗规范：卫
7、生部胃癌诊疗规范上消化道造影：气钡双重对比造影检查是诊断胃癌的常用影像学方法，对疑幽门梗阻者建议使用水溶性造影剂 胸部X线检查：应包括正侧位相超声检查：对评价胃癌局部淋巴结转移情况及表浅部位的转移有一定价值，可作为术前分期的初步检查方法。但对操作者的依赖性较强，重复性欠佳影像学检查（影像学检查（2）ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范PET-CT：对判断腹膜转移的价值有待进一步明确，目前不推荐常规使用。对常规影像学检查无法明确的转移性病灶，可酌情使用骨扫描：不推荐常规使用，对怀疑有骨转移的胃癌患者，可考虑骨扫描检查ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范诊断与分期诊断与分期 i
8、n NCCN 2011.v.11. CT/US pelvis (females) 中国专家意见：中国专家意见：should be added 3. Feasibility and necessity of meta biopsy? 中国专家意见：必要时中国专家意见：必要时 2. PET scan not feasible in china中国专家意见：中国专家意见：should be optional 强调 HER2 Test in Metastatic Disease距肿瘤组织5厘米距肿瘤组织4厘米根治手术切缘AJCC第6版ESMOAJCC第7版NCCN分期距肿瘤组织5厘米距肿瘤组织4厘米根
9、治手术切缘AJCC第6版ESMOAJCC第7版NCCN分期2010200219975th edition6th edition7th edition 国际抗癌联盟国际抗癌联盟International Union Against Cancer，UICC国际抗癌联盟肿瘤国际抗癌联盟肿瘤TNM分期分期 美国癌症联合委员会美国癌症联合委员会 American Joint Committee on Cancer, AJCC AJCC癌症分期手册癌症分期手册T 分期变化6 6thth Edition Edition7 7thth Edition EditionT1T1粘膜层粘膜层 Mucosa Muco
10、saT1aT1a粘膜下层粘膜下层 Submucosa SubmucosaT1bT1bT2aT2a肌层肌层 Muscl. Propria Muscl. PropriaT2T2T2bT2b浆膜下层浆膜下层 Subserosa SubserosaT3T3T3T3浆膜层浆膜层 Serosa SerosaT4aT4aT4T4邻近脏器邻近脏器 Invasion InvasionT4bT4bMucosaMucosaSubmucosaSubmucosaMuscl. PropriaMuscl. PropriaSubserosaSubserosa粘膜肌层浆膜表面自由腹腔邻近脏器T1T2T3T46th 7th 6t
11、h 7th 6th 7th 6th 7th N 分期变化6th Edition7th EditionN0N00 0N0N0N1N11-21-2N1N13-63-6N2N2N2N27-157-15N3aN3aN3N31616N3bN3bM 分期取消 Mx 的定义 (远处转移无法评估)2010年年CSCO年会年会早期胃癌且无淋巴结转移证据，可根据侵犯深度考虑内镜下治疗或手术治疗，术后无需辅助放疗或化疗EMR或ESD适应证为高分化或中分化无溃疡直径在2 cm内无淋巴结转移的黏膜内癌ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范身体状况身体状况良好，有良好，有切除可能切除可能M0M1T1b姑息治疗姑息
12、治疗首选多学首选多学科评估科评估T2或或T2以上以上（根据临床（根据临床分期或分期或N+）手术手术手术手术或或术前化疗（术前化疗（1类）类）或或术前化放疗术前化放疗（2b类类) 手术手术T1b-T3：足够的胃切除以达到显微镜下切缘阴性（一般距肿瘤边缘5cm）远端胃切除术胃次全切除术全胃切除术T4肿瘤需要将累及组织整块切除常规或预防性脾切除无必要。当脾脏或脾门受累时可以考虑脾切除术阳性切缘定义*：肿瘤距切缘小于1mm或电刀切缘可见癌细胞 * 卫生部胃癌诊疗规范卫生部胃癌诊疗规范建议外科医师根据局部解剖和术中所见，分组送检淋巴结，有利于淋巴结引流区域的定位在未接到手术医师分组送检医嘱或标记的情况下
13、，病理医师按照以下原则检出标本中的淋巴结：l全部淋巴结均需取材l建议术前未接受治疗病例的淋巴结总数应15枚l所有肉眼阴性的淋巴结应当完整送检l肉眼阳性的淋巴结可部分切取送检ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范NCCN指南: 淋巴结清扫范围应包括区域淋巴结-胃周淋巴结（D1）和腹腔干周围同名血管的淋巴结（D2），且至少切除15枚淋巴结ESMO指南对淋巴结的清扫范围和数目同NCCN指南全身状况恶化无法耐受手术局部浸润过于广泛己无法切除己有远处转移的确切证据，包括多发淋巴结转移、腹膜广泛播散和肝脏多灶性（3个以上）转移等心、肺、肝、肾等重要脏器功能有明显缺陷，严重的低蛋白血症和贫血、营养不
14、良无耐受手术之可能者ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范Acknowledgement of AJCC 2010 Staging Modifications公认采用AJCC 7.0版，但关于EGJ的分期如何划分东西方存在争议GAST-3: A new page, outlining post surgery therapy for pts not receiving preop中国多数患者术前未行新辅助治疗，术后治疗有规可依Principles of Endoscopic Therapy:Role of endoscopic mucosal resection for T1a tum
15、ors内镜的诊断、分期、早期癌切除及营养路径置入Pathologic review: inclusion of HER2 testing明确内镜标本、手术标本的取材要求、描述，从大体标本到病理组织学均细化规定，要求描述新辅助治疗疗效等美国美国NCCN 2011.v.1 更新更新 外科部分外科部分Positive peritoneal cytology is now Stage 4: Surgery NOT recommended 不能切除的，不能切除的，初始治疗后再初始治疗后再评估是否能够评估是否能够切除切除!局部进展期胃癌或伴有淋巴结转移的早期胃癌应采取以手术为主的综合治疗根据肿瘤侵犯深度及
16、是否伴有淋巴结转移，可考虑直接进行根治性手术或术前先行新辅助化疗，再考虑根治性手术成功实施根治性手术的局部进展期胃癌，需根据术后病理分期决定辅助治疗方案（辅助化疗，必要时考虑辅助化放疗）ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范分为新辅助化疗、辅助化疗和姑息化疗应严格掌握临床适应证应充分考虑患者病期、体力状况、不良反应、生活质量及患者意愿，避免治疗过度或治疗不足应及时评估化疗疗效，密切监测及防治不良反应，并酌情调整药物和（或）剂量疗效评价标准可参照RECIST疗效评价标准或WHO实体瘤疗效评价标准不良反应评价标准参照NCI-CTC标准鼓励患者在有资质的单位参加临床研究鼓励患者在有资质的单位
17、参加临床研究ref：卫生部胃癌诊疗规范：卫生部胃癌诊疗规范除特别注明外，卡除特别注明外，卡培他滨可替代静脉培他滨可替代静脉输注输注5FU!静脉输注静脉输注5FU优于推注优于推注全身化疗原则全身化疗原则有争议有争议术前降期增加R0切除率体内药敏 清除亚临床病灶改善预后预防医源性播散优点风险：风险：诱导诱导患者耐药患者耐药可手术切除患者疾病进展，失去手术机会可手术切除患者疾病进展，失去手术机会可切除胃癌的辅助治疗可切除胃癌的辅助治疗手术切除手术切除术后治疗术后治疗手术结果手术结果R0切除切除M1观察或对观察或对部分患者给予化放疗部分患者给予化放疗（以（以氟尿嘧啶类氟尿嘧啶类为基础）或者为基础）或者
18、对术前用对术前用ECF化疗的患者再用化疗的患者再用ECF方案（方案（1类）类）姑息治疗姑息治疗（见（见GAST-5）放疗（放疗（45-50.4 Gy）+同时予同时予 5-FU 为基础的放疗增敏（首为基础的放疗增敏（首选）选）+ 5-FU 甲酰四氢叶酸甲酰四氢叶酸R1切除切除R2切切除除Tis或或T1，N0T2，N0T3，T4或或任何任何T，N+观察观察放疗（放疗（45-50.4 Gy）+同时予同时予 5-FU 为基础的放为基础的放疗增敏（首选）疗增敏（首选）+ 5-FU 甲酰四氢叶酸甲酰四氢叶酸 或或卡卡培他滨或培他滨或ECF方案（方案（1类）类）随访（见随访（见GAST-5）随访（见随访（见
19、GAST-5）放疗（放疗（45-50.4 Gy）+ 同时予同时予5-FU 为基础为基础 的放疗增敏的放疗增敏 或或化疗化疗或最佳支持治疗（身体状况差或最佳支持治疗（身体状况差的患者）的患者）20102011年中国专家不推荐中国专家不推荐术前:顺铂5FU含卡培他滨方案上升为术前放化疗一类证据DOX和伊利替康进入术前放化疗2B术后:推荐5FULv 在输注5FU前后或卡培他滨联合放疗紫杉醇5FU进入术后放化疗推荐Version 2.2010, 02/26/10 2010 National Comprehensive Cancer Network, Inc. All rights reserved.
20、These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.N C C NPractice Guidelinesin Oncology v.2.2010Guidelines IndexGastric Cancer Table of ContentsStaging, Discussion, ReferencesGastric CancerPRINCIPLES OF SYSTEMIC THERAPY FOR GASTRI
21、COR GASTROESOPHAGEAL JUNCTIONADENOCARCINOMA (1 of 2)Note: All recommendations are category 2A unless otherwise indicated.Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.GAST-C(1 of 2)For m
22、etastatic gastric or gastroesophageal junction adenocarcinoma, some regimens listed below represent institutional preferen ces andmay not be superior to the category 1 regimens.Please refer to the original reports for specifiPlease refer to the Principles of Radiation Therapy for the radiation thera
23、py administration details.Prior to recommending chemotherapy, the requirements for the adequacy of organ function and performance status should be met.The schedule, toxicity, and potential benefits from chemotherapy should be thoroughly discussed with the patient andPatienteducation should also incl
24、ude the discussion of precautions and measures to reduce the severity and duration of complications.During chemotherapy, patients should be observed closely, treated for any complications, and appropriate blood work should bemonitored.Upon completion of chemotherapy, patients should be evaluated for
25、 response and any long-term complications., and dose modifications.caregivers.c toxicity, doses, schedule()GAST-DReferences on next pageMetastatic or Locally Advanced Cancer(where chemoradiation is not recommended):DCF (Docetaxel, cisplatin and 5-FU) (category 1)ECF (category 1)ECF modifications (ca
26、tegory 1)Irinotecan plus cisplatin (category 2B)Oxaliplatin plus fluoropyrimidine (5-FUor capecitabine) (category 2B)DCF modifications (category 2B)Irinotecan plus fluoropyrimidine (5-FU or capecitabine) (category 2B)Paclitaxel-based regimen (category 2B)Trastuzumab672,8,910,118,122,13,14,1516,17,18
27、Preoperative and Postoperative ChemotherapyPreoperative ChemoradiationPostoperative Chemoradiation(GE junction adenocarcinoma included):ECF (Epirubicin, cisplatin and 5-FU) (category 1)ECF modifications (category 1):Docetaxel or paclitaxel plus fluoropyrimidine(5-FU or capecitabine) (category 2B)Cis
28、platin plus fluoropyrimidine (category 2B)(GE junction adenocarcinoma included)Fluoropyrimidine (5-FU or capecitabine) (category 1)11,2345Leucovorin is indicated with certain infusional 5-FU-based regimens.Used in combination with systemic chemotherapy for the treatment of patients with advanced gas
29、tric cancer or GE junction adenoc arcinoma that is HER-2-positive asdetermined by a standardized method.2010版Version 2.2010, 02/26/10 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express wri
30、tten permission of NCCN.N C C NPractice Guidelinesin Oncology v.2.2010Guidelines IndexGastric Cancer Table of ContentsStaging, Discussion, ReferencesGastric CancerPRINCIPLES OF SYSTEMIC THERAPY FOR GASTRICOR GASTROESOPHAGEAL JUNCTIONADENOCARCINOMA (1 of 2)Note: All recommendations are category 2A un
31、less otherwise indicated.Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.GAST-C(1 of 2)For metastatic gastric or gastroesophageal junction adenocarcinoma, some regimens listed below repres
32、ent institutional preferen ces andmay not be superior to the category 1 regimens.Please refer to the original reports for specifiPlease refer to the Principles of Radiation Therapy for the radiation therapy administration details.Prior to recommending chemotherapy, the requirements for the adequacy
33、of organ function and performance status should be met.The schedule, toxicity, and potential benefits from chemotherapy should be thoroughly discussed with the patient andPatienteducation should also include the discussion of precautions and measures to reduce the severity and duration of complicati
34、ons.During chemotherapy, patients should be observed closely, treated for any complications, and appropriate blood work should bemonitored.Upon completion of chemotherapy, patients should be evaluated for response and any long-term complications., and dose modifications.caregivers.c toxicity, doses,
35、 schedule()GAST-DReferences on next pageMetastatic or Locally Advanced Cancer(where chemoradiation is not recommended):DCF (Docetaxel, cisplatin and 5-FU) (category 1)ECF (category 1)ECF modifications (category 1)Irinotecan plus cisplatin (category 2B)Oxaliplatin plus fluoropyrimidine (5-FUor capeci
36、tabine) (category 2B)DCF modifications (category 2B)Irinotecan plus fluoropyrimidine (5-FU or capecitabine) (category 2B)Paclitaxel-based regimen (category 2B)Trastuzumab672,8,910,118,122,13,14,1516,17,18Preoperative and Postoperative ChemotherapyPreoperative ChemoradiationPostoperative Chemoradiati
37、on(GE junction adenocarcinoma included):ECF (Epirubicin, cisplatin and 5-FU) (category 1)ECF modifications (category 1):Docetaxel or paclitaxel plus fluoropyrimidine(5-FU or capecitabine) (category 2B)Cisplatin plus fluoropyrimidine (category 2B)(GE junction adenocarcinoma included)Fluoropyrimidine
38、(5-FU or capecitabine) (category 1)11,2345Leucovorin is indicated with certain infusional 5-FU-based regimens.Used in combination with systemic chemotherapy for the treatment of patients with advanced gastric cancer or GE junction adenoc arcinoma that is HER-2-positive asdetermined by a standardized
39、 method.Version 2.2010, 02/26/10 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.N C C NPractice Guidelinesin Oncology v.2.2010Guidelines IndexGastric Cancer
40、Table of ContentsStaging, Discussion, ReferencesGastric CancerPRINCIPLES OF SYSTEMIC THERAPY FOR GASTRICOR GASTROESOPHAGEAL JUNCTIONADENOCARCINOMA (1 of 2)Note: All recommendations are category 2A unless otherwise indicated.Clinical Trials: NCCN believes that the best management of any cancer patien
41、t is in a clinical trial. Participation in clinical trials is especially encouraged.GAST-C(1 of 2)For metastatic gastric or gastroesophageal junction adenocarcinoma, some regimens listed below represent institutional preferen ces andmay not be superior to the category 1 regimens.Please refer to the
42、original reports for specifiPlease refer to the Principles of Radiation Therapy for the radiation therapy administration details.Prior to recommending chemotherapy, the requirements for the adequacy of organ function and performance status should be met.The schedule, toxicity, and potential benefits
43、 from chemotherapy should be thoroughly discussed with the patient andPatienteducation should also include the discussion of precautions and measures to reduce the severity and duration of complications.During chemotherapy, patients should be observed closely, treated for any complications, and appr
44、opriate blood work should bemonitored.Upon completion of chemotherapy, patients should be evaluated for response and any long-term complications., and dose modifications.caregivers.c toxicity, doses, schedule()GAST-DReferences on next pageMetastatic or Locally Advanced Cancer(where chemoradiation is
45、 not recommended):DCF (Docetaxel, cisplatin and 5-FU) (category 1)ECF (category 1)ECF modifications (category 1)Irinotecan plus cisplatin (category 2B)Oxaliplatin plus fluoropyrimidine (5-FU or capecitabine) (category 2B)DCF modifications (category 2B)Irinotecan plus fluoropyrimidine (5-FU or capeci
46、tabine) (category 2B)Paclitaxel-based regimen (category 2B)Trastuzumab672,8,910,118,122,13,14,1516,17,18Preoperative and Postoperative ChemotherapyPreoperative ChemoradiationPostoperative Chemoradiation(GE junction adenocarcinoma included):ECF (Epirubicin, cisplatin and 5-FU) (category 1)ECF modific
47、ations (category 1):Docetaxel or paclitaxel plus fluoropyrimidine(5-FU or capecitabine) (category 2B)Cisplatin plus fluoropyrimidine (category 2B)(GE junction adenocarcinoma included)Fluoropyrimidine (5-FU or capecitabine) (category 1)11,2345Leucovorin is indicated with certain infusional 5-FU-based
48、 regimens.Used in combination with systemic chemotherapy for the treatment of patients with advanced gastric cancer or GE junction adenocarcinoma that is HER-2-positive asdetermined by a standardized method.S1 monotherapystage II/III gastric cancer patients (Japanese pts) after curative D2 gastrecto
49、mySurvival benefit of S1+surgery group over surgery aloneCLASSIC study (international trial)Stage II/III, after curative D2 gastrectomy (Korean and Chinese pts )Capecitabine+oxaliplatin Well tolerated, and significant DFS improvement, survival data is under follow upARTIST study (ongoing) stage Ib (
50、T2bN0) - IV (M1 excluded), after curative D2 gastrectomyCompare XP vs XP + radiotherapy (RT)Well tolerated, and survival data is under follow upECF or modified ECF after curative resection?FP from FFCD 9703 study 辅助化疗推荐氟尿嘧啶加铂类的联合方案 新辅助（术前）化疗推荐ECF及改良方案，术后根据术分期及新辅助疗效延续或酌情调整方案2011 卫生部胃癌诊疗规范可手术胃癌的术前、术后化
