1、Multidisciplinary Management of Gastric Cancer and Colorectal CancerXianglin YuanOncology Department ofTongji HospitalCancer treatmentchemotherapysurgery Targeted therapy Endocrine therapy-radiotherapy Multidisciplinary Management surgerychemotherapyradiotherapy Targeted therapy Endocrine therapy- M
2、ultidisciplinary Management What kind of treatment is suitable?What kind of combination is the most suitable?When should the treatment be suggested?what drugs?Why-?Real time ,reasonable treatment , real patient!5W and 3R ContentsMultidisciplinary Management Multidisciplinary Management of Gastric Ca
3、ncerof Gastric Cancer ContentsMultidisciplinary Management Multidisciplinary Management of Gastric Cancerof Gastric Cancer2. Multidisciplinary Management of 2. Multidisciplinary Management of Colorectal CancerColorectal Cancer胃癌术后的预后胃癌术后的预后分期分期研究组研究组病例数病例数分分 期期IAIBIIIIIAIIIBIV Hundahl (美国美国)50169715
4、63718115 Siewert (德国德国)1654866955381716 Wanebo (美国美国)183655029133 Kim (韩国韩国)1078393846946309 Hayashi (日本日本)94095.877.751.230.114.86.2 Morowaki (日本日本)146898.497.86548.335.515.9 詹友庆詹友庆 (中国中国)256186.858.728.47.6 Multidisciplinary Management Principle of treatment neoadjuvant and adjuvant therapy System
5、ic therapy for Metastatic or Locally Advanced Cancer Target therapy RadiotherapyOperable Disease: StagingLocal assessmentEndoscopy (diagnostic)EUS Local staging and assessing proximal & distal extent of (OGJ) tumour Staging accuracy 75% in gastric cancerAssessment for distal diseasel CT Thorax/abdom
6、en/pelvisl Laparoscopy identifies CT occult metastatic diseaseImprove selection of patients for radical RxPET can provide additional information regarding local and distal diseaseless sensitive but more specific than CT for local LN metastaseslimitation 30% of gastric cancer are non-FDG avidpotentia
7、l role for early response assessment to neo-adjuvant Rx1. Abdalla & Pisters, Seminars in Oncology 2004 2. Kim et al, Eur J Nucl Med Mol Imaging 2006 3. Ott et al., Clin Cancer Res 2008 EvaluationlDetermine extent of disease with CT scan EUSlLaparoscopylPeritoneal cytology if visible peritoneal impla
8、nts is absentlLaparoscopic staging with peritoneal washings for patients with advanced tumors, clinical T3 or N+ disease Evaluation-患者分类患者分类可手术可手术但身体状态不适合手术潜在可手术不能手术只能姑息治疗 Multidisciplinary Team 以手术为主的综合治疗早期可单独手术中期手术为主， 辅以放化疗晚期患者化疗为主不能耐受手术者 姑息治疗 Criteria of unresectability for curelLocoregionally ad
9、vancedlLevel 3 or 4 lymph node highly suspicious on imaging or confirmed by biopsylInvasion or encasement of major vascular structureslDistant metastasis or peritoneal seeding (including positive peritoneal cytology)Peri-operative ChemotherapyPeri-operative Chemotherapy:The MRC MAGIC TrialPeri-opera
10、tive Rx:1. Boige et al., ASCO 2007 2. Cunningham et al., NEJM 2006 Indications of Surgery Indications of perioperative treatmentThe number of detected lymph nodes is asked to be more than 15. SurgerylEarly stage：partial gastric resection or gastectomylAdvanced stage（M0）：）： Radical gastectomy （D2）or
11、extended radical gastectomylAdvanced stage （M1，medical unfit，or with obstruction and bleeding）：）： Palliative gastric resection, gastrojejunostomy or gastrostomy Surgery- - Resectable tumorslTis or T1a：may be candidates for EMRlT1b-T3 : Adequate resection (typically 4 cm from tumor)Distal gastrectomy
12、Subtotal gastrectomyTotal gastrectomylT4 ：en bloc resection of involved structures Surgery-Regional lymphatics resectionPrimary tumor locationSurgeryresectionLymph nodes Proximal gastric cancerD11，2，3，4sa，4sbD21，2，3，4sa，4sb，4d，7，8a，9，10，11p，11d，110Middle gastric cancerD11，3，4sb，4d，5，6D21，3，4sb，4d，5，
13、6，7，8a，9，11p，12aDistal gastric cancerD13，4d，5，6D23，4d，5，6，1，7，8a，9，11p，12a，14vThe number of detected lymph nodes is asked to be more than 15.What kind of treatment should be suggested according to the pathological reports after surgery? Multidisciplinary Management Principle of treatment adjuvant th
14、erapy Systemic therapy for Metastatic or Locally Advanced Cancer Target therapy Radiotherapy术后辅助治疗术后辅助治疗争议所在？争议所在？日本日本ACTS-GC研究研究期及期及期胃癌期胃癌D2手手术术3年生存率术后辅年生存率术后辅助化疗组助化疗组80.1%，单，单纯手术组纯手术组70.1%。3年年OS5年年OSXELOX (n=520)83%78%术后观察组术后观察组(n=515)78%69%HR=0.66 ；95% CI：0.51-0.85CLASSIC 研究：研究： XELOX方案可带来总生存方案可带
15、来总生存OS获益获益ITT 人群 ；中位随访时间: 62.4个月分层因素：国家，疾病分期3年：Bang YJ, et al. Lancet. 2012 Jan 28; 379(9813): 315-321.5年：Sung Hoon Noh, WCGIC, 2013 时间 (月)1.00.80.60.40.2006121830364854606678244272OS3年绝对差值5%p=0.04935年绝对差值9%p=0.0015XELOX (n=520)术后观察组术后观察组(n=515) R0 resection without perioperative treatment lTis or T
16、1，N0：observelT2，N0：observe 5-FU CF or Capecitabine， then 5-FU CF or Capecitabine for selected patientslT3，T4，Any N or Any T，N+ ：5-FU CF or Capecitabine， then 5-FU-based chemoradiation， then 5-FU CF or Capecitabine for selected patients单药替吉奥（S1 ）XELOX方案 R0 resection with perioperative treatment lT2，N
17、0：observe or 5-FU CF or Capecitabine， then 5-FU CF or Capecitabine for selected patients or ECF or its modification if received preoperativelylT3，T4，Any N or Any T，N+ ：5-FU CF or Capecitabine， ， the 5-FU CF or Capecitabine for selected patients or ECF or its modification if received preoperatively R
18、1 resection without perioperative treatment lChemoradiation （Fluoropyrimidine-based） R2 resection without perioperative treatment l Chemoradiation （Fluoropyrimidine-based）or l Chemotherapyorl Best support careRadioation therapyA. Proximal one-third/Cardia/ Esophagogastric Junction PrimariesB. Middle
19、 one-third/Body PrimariesC. Distal one-third/Antrum/Pylorus PrimariesDose：45-50.4 Gy (1.8 Gy/day)LAND MARK-INT 0116Macdonald JS, et al. NEJM, 345:725,2001.高危高危T3-4，N+，R1, 需助放化疗需助放化疗ARTIST结果：对于淋巴结阳性患者获益treatmentNevent1224364860XP/XRT/XP230552144495355XP118721539566770treatmentNevent1224364860XP/XRT/X
20、P203491942454749XP193661437516265总人群总人群DFS淋巴结阳性淋巴结阳性DFSJeeyun Lee ,et; J Clin Oncol 30:268-273.2012新进展高危高危T3-4，N+，R1, 需助放化疗需助放化疗 Multidisciplinary Management Principle of treatment neoadjuvant and adjuvant therapy Systemic therapy for Metastatic or Locally Advanced Cancer Target therapySystemic ther
21、apy for Metastatic or Locally Advanced Cancer （where where chemoradiation is not indicated）A. First-Line TherapyB. Second-Line TherapyC. Alternative regimens to be consideredMetastatic Gastric CancerSystemic therapy for Metastatic or Locally Advanced Cancer （where where chemoradiation is not indicat
22、ed）First-Line TherapylTrastuzumab with chemotherapy lDCF and DCF modificationslECF and ECF modificationslFluoropyrimidine and cisplatinlFluoropyrimidine and oxaliplatinlFluoropyrimidine and irinotecanlPaclitaxel with cisplatin or carboplatinlDocetaxel with cisplatinlDocetaxel and irinotecan (categor
23、y 2B)lFluoropyrimidine (5-FU or capecitabine)lDocetaxel or paclitaxelSurvival: ECF v EOXToGA-ResultsMOS13.8vs11.1MPFS6.7vs5.5Systemic therapy for Metastatic or Locally Advanced Cancer （where where chemoradiation is not indicated）Second-Line TherapyDependent on prior therapy and PS:lTrastuzumab with
24、chemotherapy lIrinotecan and cisplatinlIrinotecan and fluoropyrimidinelIrinotecan and docetaxel lIrinotecan and mitomycin lDocetaxel or paclitaxel lIrinotecan Systemic therapy for Metastatic or Locally Advanced Cancer （where where chemoradiation is not indicated）Alternative regimens to be considered
25、lGemcitabine, 5-FU and leucovorinlPegylated liposomal doxorubicin, cisplatin and 5-FUlMitomycin and irinotecanlMitomycin, cisplatin, and 5-FUlMitomycin and 5-FUlEtoposidelErlotiniblCetuximab小小 结结 手术是早中期胃癌的首选治疗方法手术是早中期胃癌的首选治疗方法 D2为标准的手术方式为标准的手术方式 术后化疗可提高生存术后化疗可提高生存 XELOX 方案是目前相对标准术后化疗方案方案是目前相对标准术后化疗方
26、案小小 结结 目前晚期患者无公认标准的化疗方案（，目前晚期患者无公认标准的化疗方案（，DCF，XELOX) 以以5-FU类为基础的化疗（，类为基础的化疗（，DF）是胃癌综合治疗的重要方式）是胃癌综合治疗的重要方式 放射治疗有重要作用放射治疗有重要作用高危高危T3-4，N+，R1, 需助放化疗需助放化疗靶向治疗有一定的作用靶向治疗有一定的作用 （贺赛汀对（贺赛汀对 Her-2阳性患者科提高疗效）阳性患者科提高疗效）2 病例病例 Contents1. Multidisciplinary Management 1. Multidisciplinary Management of Gastric Ca
27、ncerof Gastric Cancer Colorectal CancerColon cancerRectal cancerColon cancerAdjuvant Chemotherapy for Resectable Colon Cancer Staging% at diagnosis5-year survival 15%85-95%20-30%60-80%30-40%30-60%20-25%5%Adjuvanttherapy Multidisciplinary Management Principle of treatment neoadjuvant and adjuvant the
28、rapy Systemic therapy for Metastatic or Locally Advanced Cancer Target therapy Radiotherapy Staging workup l Pathologic tissue reviewPathologic tissue reviewl Total colonoscopyTotal colonoscopyl Complete blood count, platelets, chemistry profileComplete blood count, platelets, chemistry profilel Car
29、cinoembryonicCarcinoembryonic antigen (CEA) determination antigen (CEA) determinationl Baseline CT scans of the chest, abdomen and Baseline CT scans of the chest, abdomen and pelvis.pelvis.l PET scan is not routinely indicated at baseline, and PET scan is not routinely indicated at baseline, and sho
30、uld not be done as a matter of general should not be done as a matter of general surveillancesurveillance Potential results of staging workup l Colon cancer appropriate for resection Colon cancer appropriate for resection （non non metastaticmetastatic）l Suspected or proven Suspected or proven metast
31、aticmetastatic adenocarcinomaadenocarcinoma Evaluation-患者分类患者分类可手术可手术但身体状态不适合手术潜在可手术不能手术只能姑息治疗 Multidisciplinary Team 以手术为主的综合治疗早期可单独手术中期手术为主， 辅以化疗晚期患者化疗为主加或不加靶向治疗不能耐受手术者 姑息治疗 Surgery selection l ResectableResectable nonobstructingnonobstructing： ColectomyColectomy with en with en bloc removal of re
32、gional lymph nodesbloc removal of regional lymph nodesl ResectableResectable obstructing obstructing: One-stage : One-stage colectomycolectomy with with en bloc removal of regional lymph nodes or en bloc removal of regional lymph nodes or Resection with diversion or in stages Resection with diversio
33、n or in stages managmentmanagmentWhat kind of treatment should be suggested according to the pathological reports after surgery? Multidisciplinary Management Principle of treatment adjuvant therapy Systemic therapy for Metastatic or Locally Advanced Cancer Target therapy目 录根治术后是否必须根治术后是否必须做辅助治疗？做辅助治
34、疗？ 辅助化疗是否能获得生存获益？辅助化疗是否能获得生存获益？ 辅助化疗的获益人群？辅助化疗的获益人群？化疗方案如何选择？化疗方案如何选择？ 疗效与安全性疗效与安全性 老年患者辅助化疗老年患者辅助化疗辅助化疗的时机和辅助化疗的时机和疗程的选择？疗程的选择？ 术后多久开始化疗最佳？术后多久开始化疗最佳？ 化疗时间多久为宜？化疗时间多久为宜？术后如何随访？术后如何随访？复发风险在术后2年最高Sargent D, et al. J Clin Oncol. 2009; 27(6): 872 7.5年的复发风险年的复发风险8年的复发风险年的复发风险4个月患者DFS和OS优于4个月患者结论：结肠癌术后至少
35、应该辅助化疗4个月以上辅助化疗时间辅助化疗时间患者患者3年年DFS4个月114(52.8%)79.4%条件可行，术后辅助化疗应该尽早开始 10个研究 n=15,410荟萃分析： TTAC*增加4周，总生存降低14结果：Biagi JJ, et al. Association Between Time to Initiation of Adjuvant Chemotherapy and Survival in Colorectal Cancer JAMA. 2011; 305(22): 2335-2342* TTAC（time to adjuvant chemotherapy） Multidis
36、ciplinary Management Principle of treatment adjuvant therapy Systemic therapy for Metastatic or Locally Advanced Cancer Target therapyCHEMOTHERAPY FOR ADVANCED OR METASTATIC DISEASE20.621.320.319.517.414.814.112.60510152025Saltz, NEJM 20005-FU 推注Douillard, Lancet 20005-FU静滴Saltz, NEJM 2000IFLDouilla
37、rd, Lancet 2000FOLFIRIGoldberg, JCO 2004FOLFOXHurwitz, NEJM 2004IFL + 贝伐珠单抗Tournigand, JCO 2004FOLFIRI 后序贯FOLFOXDouillard, JCO 2009FOLFOX + 帕尼单抗VanCutsem, NEJM 2009FOLFIRI + 西妥昔单抗OS (月)Saltz JCO 2008FOLFOX + 贝伐珠单抗23.923.5组别临床表现治疗目标组 0可完全切除(R0切除)的肝和/或肺转移治愈，降低复发风险组 1不可R0切除的肝和/或肺转移，化疗后可能可切除最大程度缩小瘤体组 2多
38、发性转移，进展迅速和/或有肿瘤相关症状尽快获得缩小瘤体的临床效果, 控制疾病进展组 3多发性转移，无法手术切除，起始无症状，侵袭性疾病少防止疾病进一步进展2012 ESMO 共识：mCRC分组治疗Schmoll H-J, et al. Ann Oncol 2012;23:24792516以治愈为目标术后予以与辅助相同治疗转化治疗能将初始不可手术的肝转移转化为以根治为目的可手术肝转移转化率转化率: : 12.5%12.5%30%总总切除切除: : 453453例例335335化疗化疗: 1: 1439439例例患者中患者中11041104例例(74%)(74%)进行转化治疗进行转化治疗Adam
39、R, et al. Ann Surg 2004;240:644658Adam R, et al.Ann Oncol 2003;14: ii13-ii16 肝转移初始切除或化疗后切除后生存率相似肝转移初始切除或化疗后切除后生存率相似手术切除的肝转移患者长期生存与III期患者相当0 00.50.51 11.51.52 22.52.53 33.53.54 44.54.55 51 10.90.90.80.80.70.70.60.60.50.50.40.40.30.30.20.20.10.10 0生存率生存率时间（年）时间（年）所有所有期期所有患者所有患者所有所有期期期中手术切除的肝转移患者期中手术切除
40、的肝转移患者n=3116n=3116Morris EJ, et al. Br J Surg. 2010;97(7):1110-8.Morris EJ, et al. Br J Surg. 2010;97(7):1110-8.19981998-2004-2004年间诊断为结直肠癌的患者：年间诊断为结直肠癌的患者：5 5年生存率年生存率（n=114,155n=114,155）7272 Suspected or proven Any T, any N, M1Synchronous liver only and/or lung only metastasesResectable： Colectomy,
41、 with synchronous or staged liver or lungresectionorNeoadjuvant therapy (for 2-3 months) followed by synchronous or staged colectomy and resection ofmetastatic diseaseorColectomy, followed by chemotherapy (for 2-3 months)and staged resection of metastatic disease Suspected or proven Any T, any N, M1
42、Synchronous liver only and/or lung only metastasesUnresectable (potentially convertible or unconvertible) Systemic therapy and consider colon resection only ifimminent risk of obstruction or significant bleedingthen re-evaluate for conversion to resectable every 2 mo Suspected or proven Any T, any N
43、, M1Synchronous abdominal/peritoneal metastasesNonobstructingChemotherapy Obstructed or imminent obstructionColon resection or Diverting colostomy orBypass of impending obstruction or Stenting，then chemotherapy荟萃分析荟萃分析: :联合奥沙利铂联合奥沙利铂和和伊立替康疗效相似伊立替康疗效相似StudyStudyYeaYear rPatient Patient numbernumbers
44、sMedian Median PFS/TTPFS/TTP PMedian Median OSOSWeighted Weighted PFS PFS averageaverageWeighted Weighted OS OS averageaverageDouillardDouillard2002000 01991996.7 mo6.7 mo17.4 17.4 momo7.6 mo7.6 mo18.9 mo18.9 moTournigandTournigand2002004 41131138.5 mo8.5 mo20.9 20.9 momoColucciColucci2002005 516416
45、47.0 mo7.0 mo14.0 14.0 momoKohneKohne2002005 52142148.5 mo8.5 mo20.1 20.1 momoFuchs (BICC)Fuchs (BICC)2002007 71441447.6 mo7.6 mo23.1 23.1 momode de GramontGramont2002000 02102109.0 mo9.0 mo16.2 16.2 momo8.2 mo8.2 mo18.2 mo18.2 moEnd End PointPointFOLFIFOLFIRIRIFOLFFOLFOXOXP-P-valuevalueRRRR56565454
46、.26.26TTPTTP8.58.58.08.0.26.26OSOS21.521.520.620.6.99.99TournigandTournigand C, et al. J C, et al. J ClinClin OncolOncol 2004; 22: 229-237 2004; 22: 229-237V308V308研究显示研究显示FOLFOX/FOLFIRIFOLFOX/FOLFIRI互为一二线疗效相似互为一二线疗效相似OSOS疗效疗效 FOLFOX FOLFIRI毒性毒性 FOLFOX: 神经毒性、嗜中性粒细胞减少 FOLFIRI: 消化道毒性、脱发CPT-11OXA治疗的选择与
47、困惑治疗的选择与困惑5-FUBevacizumabCetuximabPanitumumabBevacizumabCetuximabPanitumumab Multidisciplinary Management Principle of treatment neoadjuvant and adjuvant therapy Systemic therapy for Metastatic or Locally Advanced Cancer Target therapy RadiotherapyLocally unresectable or medically inoperableor metat
48、asis or recurrence Patient appropriate for intensive therapy：Chemotherapy+ molecular-targeted drugs（FOLFOX，CapeOX，FOLFIRI，FOLFOXIRI， 5-FU/leucovorin or Capecitabine） （bevacizumab，panitumumab）Patient not appropriate for intensive therapy：Infusional 5-FU + leucovorin or Capecitabine bevacizumab or Cet
49、uximab or PanitumumabCRYSTAL - Relating KRAS status to efficacy: PFSVan Cutsem E et al. Proc Am Soc Clin Oncol. 2007. Abstract 4000.Randomised trials of EGFR antibodies 1st line k-ras wt only1st Line mCRCTrialTherapyORRPFS (mo)OS (mo)CRYSTAL(n=666) *FOLFIRI+/- Cetux* 40% vs. 57% 8,4 vs. 9,9HR = 0,69
50、6 20.0 vs.23,5HR = 0,796PRIME(n=656) *FOLFOX+/- Pani* 48% vs. 57% 10,0 vs.8,6HR = 0,80( )19,7 vs. 23,9HR = 0.88OPUS(n=197) *FOLFOX+/- Cetux* 34% vs. 57% 7,2 vs.8,3HR = 0,567( )18,5 vs.22,8HR = 0,855COIN(n=729) *XELOX/FOLFOX +/- Cetux* 57% vs. 64%8,6 vs.8,6HR = 0,95917,9 vs.17,0HR = 1,038NORDIC(n=194
