结直肠癌新辅助治疗（含肝转移）

null结直肠癌患者新辅助治疗结直肠癌患者新辅助治疗北京大学肿瘤医院 消化肿瘤内科直肠癌术前放化疗直肠癌术前放化疗新辅助治疗的目的新辅助治疗的目的提高手术切除率 提高保肛率 降低局部复发 延长患者无病生存期推荐推荐T3和/或N+的可切除直肠癌患者，推荐术前新辅助放化疗。 直肠癌术前化疗推荐以氟尿嘧啶类药物为基础的化疗 方案 气瓶 现场处置方案 .pdf气瓶 现场处置方案 .doc见习基地管理方案.doc关于群访事件的化解方案建筑工地扬尘治理专项方案下载 nullnullnullnullnullnullnullnullnullnull结肠癌肝转移术前化疗结肠癌肝转移术前化疗推荐推荐结直肠癌患者合并肝转移，可切除或者潜在可切除，推荐术前化疗或化疗联合靶向药物治疗：西妥昔单抗（推荐用于K-ras基因状态野生型患者），或联合贝伐珠单抗 化疗方案推荐FOLFOX，或者FOLFIRI，或者CapeOx， Metastatic colorectal cancerliver metastasesNot resectableresectablechemotherapy85%15%+ other locations of metastaseschemotherapy50%50%Patients with metastatic colorectal cancer5y Survival: 5%5 y survival: 5%Metastatic colorectal cancer5 y survival: 20-40%Resection rate of metastases and tumor responseResection rate of metastases and tumor responseStudies incl. selected pats. (liver metastases only, no extrahepat. disease) r=.96, p=.002Studies incl. all patients with metastatic CRC (solid line) r=.74, p<.001 Phase III studies in metastatic CRC (dashed line) r=.67, p=.024, p=.024 Folprecht … Köhne et al, Ann Oncol 2005新辅助化疗优势新辅助化疗优势患者体内化疗药物的药敏试验 清除微小转移灶 观察甄别出快速进展病例 提高R0切除率？并减少切除的正常肝组织 延长生存期？Adjuvant, neoadjuvant, conversion therapy for CRC liver metastasesAdjuvant, neoadjuvant, conversion therapy for CRC liver metastasesResectable adjuvant neo-adjuvant Unresectable Conversion chemotherapynullColorectal Ca R0 Resection of MetastasesControversy: Adjuvant Therapy ?USA Yes (Kemeny NEJM 1999)Europa No (Lorenz NEJM 2000)Liver metastases: adjuvant HAI + i.v. CTXKemeny et al NEJM 1999 and 2005Liver metastases: adjuvant HAI + i.v. CTXLV5FU vs. FOLFIRI as adjuvant therapy following resection of CLM - DFSLV5FU vs. FOLFIRI as adjuvant therapy following resection of CLM - DFS1-year DFS: 63% vs. 77% 2-year DFS: 46% vs. 51%Ychou et al. ASCO 2008Adjuvant Chemotherapy for CRC liver metastasesAdjuvant Chemotherapy for CRC liver metastases YES！ Which patients? 高复发风险 which regimen? 化疗？HAI？ 方案？FU、OXA？Target ？ EORTC phase III study 40983 研究 设计 领导形象设计圆作业设计ao工艺污水处理厂设计附属工程施工组织设计清扫机器人结构设计 EORTC phase III study 40983 研究设计RandomizeSurgeryFOLFOX4FOLFOX4Surgery6 cycles (3months)6 cycles (3 months)364 例潜在可切除肝转移 (metachronous or synchronous) ，4个以上病灶，无肝外转移nullEORTC Study 40983 CT S P 3-y FPS % 42.4 33.2 0.025不能切除的结直肠癌肝转移新辅助化疗乐沙定，伊立替康和持续滴注5-FULV(FOLFOXIRI)两周方案和Folfiri相比一线治疗转移性结直肠癌： III期临床结果（GONO）A. Falcone, et al ASCO GI 2006, #227不能切除的结直肠癌肝转移新辅助化疗null伊立替康，乐沙定和持续滴注5-FULV(FOLFOXIRI)两周方案和Folfiri相比一线治疗转移性结直肠癌：III期临床结果（GONO）* Douillard Lancet 2000 ** Masi Ann Oncol 2004临床设计FOLFIRI*CPT-11 180 mg/m2 1-h d.1 L-LV 100 mg/m2 2-h d.1,2 5FU 400 mg/m2 bolus d.1,2 5FU 600 mg/m2 22-h d.1,2 q. 2 wks x 12个周期FOLFOXIRI**CPT-11 165 mg/m2 1-h d.1 LOHP 85 mg/m2 2-h d.1 L-LV 200 mg/m2 2-h d.1 5FU 3200 mg/m2 48-h CI d.1 q. 2 wks x 12 个周期分层  中心  PS 0/1-2  辅助化疗FOLFIRI方案进展后，推荐含乐沙定的方案nullA. Falcone, ASCO GI 2006, #227*p<0.001有效率 (ITT 分析)化疗后手术切除率 (所有病人)*p<0.033疗效结果主要目标：RR 次要目标：PFS, OS, post surgical resectionsn, safety QOLRescue Surgery for Unresectable Colorectal Liver Metastases Downstaged by ChemotherapyA Model to Predict Long-term SurvivalRescue Surgery for Unresectable Colorectal Liver Metastases Downstaged by ChemotherapyA Model to Predict Long-term SurvivalRetrospective study 1104 cases with unresectable liver metastases Chemotherapy regimens：5-FU/LV/OXA or IRI or both 138(12.5%) achieved secondary curative hepatic resection Survival rate: 5-year 33% 10-year 23%Adam R et al,Ann surg.2004;240:644-657Resection of liver metastases: non-selected patients treated with targeted/cytotoxic agentsResection of liver metastases: non-selected patients treated with targeted/cytotoxic agentsFirst author N Regimen RR Resection rate Folprecht 21 Cetuximab/irinotecan 67% 19% /AIO (24%)* Diaz Rubio 43 Cetuximab/FOLFOX4 79% 19% Rougier 42 Cetuximab/FOLFIRI 45% 21% Fisher 27 Gefitinib/FOLFOX4 78% 22% Hurwitz 411 IFL 35% （<2% 412 IFL/bevacizumab 45% resection) Hoff 21 FOLFIRI/bevacizumab 70% 19% *One patient declined offered resectionUpdated information based on Folprecht et al. Ann Oncol, 2005Liver-limited disease PFS and RR in KRAS wild-type Liver-limited disease PFS and RR in KRAS wild-type aCochran-Mantel-Haenszel (CMH) testVan Cutsem, Köhne in pressnullRandomized multicenter study of cetuximab plus FOLFOX or cetuximab plus FOLFIRI in neoadjuvant treatment of non-resectable colorectal liver metastases (CELIM study) G. Folprecht,1 T. Gruenberger,2 J.T. et alPatients with non-resectable colorectal liver metastases No extrahepatic diseaseEfficacy: Confirmed ResponseEfficacy: Confirmed Response Responses confirmed by 2nd CT scan according to RECIST or by resection Chi square test for comparison between FOLFOX6+Cet vs FOLFIRI+Cet would be 0.23 ResectionsResectionsComparison of R0 resections between strata technically non-resectable and ≥ 5 liver mets: p=0.14手术前化疗时限手术前化疗时限化疗时间最佳选择时间？The relation between duration of preoperative chemotherapy and perioperative morbidityMore than 6 cycles of neoadjuvant systemic chemotherapy increase morbidity significantly Karoui et al.Ann surg.2006:243:1-7The relation between duration of preoperative chemotherapy and perioperative morbidity手术前化疗的关注问题手术前化疗的关注问题化疗时间手术最佳时间？个体化！ 及时评估疗效，预防并发症 不忘主题——手术治疗！谢谢！谢谢！