结直肠癌肝转移新辅助化疗的共识与争议.ppt
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1、结直肠癌肝转移新辅助化疗的共识与争议,第三军医大学西南医院肿瘤中心,梁后杰,Epidemiology of colorectal cancer(CRC),Results of Hepatic Resection for Metastatic Colorectal Cancer,Liver metastases of CRC,Management of MCRC: An Evolving Treatment Algorithm,Neoadj:where is the most controversy,Concept of resectability,手术的关注重点由“哪些可以切除”转变为“哪些可
2、以保留” Timothy M. Pawlik 2008,只要能够完全切除,转移灶的个数与长期生存率无关 Altendorf-Hofmann A, Scheele J. A critical review of the major indicators of prognosis after resection of hepatic metastases from colorectal carcinoma. Surg Oncol Clin N Am 2003;12:165192,No.of met and resectability,(A): 不完全性切除患者的MST只有 14 月,而完全切除患者
3、的MST为44 月。 Altendorf-Hofmann A, et al. Surg Oncol Clin N Am 2003;12:165192. (B): 只要能够完全切除,切除边界的宽度对生存时间无明显影响。 Pawlik TM, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 2005;241:715722; discussion 722724,Margin and
4、 resectability,Neoadjuvant chemotherapy for resectable liver metastases of CRC,resectable,Preoperative chemotherapy what are possible benefits?,Tumor shrinkage may facilite resection whith a hope for higher survival rates Test chemoresponsiveness of matastases Select candidates for resection -Exclud
5、e tumors progressing while on chemotherapy -Be more aggressive on responding tumors,EORTC 40983: Peri-operative chemotherapy,Size of lesions after pre-op chemotherapy,Phase 3 Trial of Perioperative FOLFOX4 and Surgery for Resectable CRC Liver Metastases (EORTC 40983):PFS,Rationale AGAINST neoadjuvan
6、t CT,Risk that metastases become unresectable if they progress during chemotherapy Uncertainty about how to deal with “complete response” to chemotherapy Liver damage induced by chemotherapy,Preoperative chemotherapy: potential problems,Lost window of opportunity Tumor growth in a critical area may
7、render metastases unresectable Chemotherapy induced portal vein thrombosis,1. Donadon M, et al. W J Gastroenteral 12:6556, 2006,Survival according to response to neoadjuvant chemotherapy,ATE:cerebral infact, myocardial infarction, TIA, angina Risk factors for developing ATE Age 65 y (P=0.01) Prior h
8、istory of ATE (P0.01) Hurwiz et al, N Engl J Med 350:2335,2004 Giantonio et al. ASCO, 2005 Cassidy et al, ESMO, 2006 Sandler et al, N Engl J Med 355:2542, 2006 Miller et al, SABCS, 2005,Bevacizumab:Arterial Thromboembolic Events complicate subsequent liver resection,Preoperative chemotherapy: potent
9、ial problems,Hinder detection of known metastases Radiographic complete response1 Frequency: 6.5% Rare if initial tumor 4.5 cm Residual tumor identified: 83% Chemotherapy reduces sensitivity of PET detection of matastases2,3 Benoist S, et al, J Clin Oncol 24:3939,2006 Akhurst T,et al, J Clin Oncol 2
10、3:8713, 2005 Tan, MCB et al, J Gastrointest Surg 11:1112, 2007,“Complete response”:does it cure?,Complete response,Preoperative chemotherapy: potential problems,Radiographic CR Pathologoc CR Radiographic CR Pathologoc CR1 Resection strategy must remove these lesions “Blind” removal sounds easy in co
11、ncept Benoist S, et al, JCO 24:3939, 2006,Chemotherapy induces liver damage The “blue” liver,The type of liver injury depends on drug administered Vascular lesions: Oxaliplatin (Rubbia-Brandt et al, 2004) Steatosis: 5FU, Irinotecan? (Parikh et al, 2003) Steatohepatitis: Irinotecan (Vauthey et al, 20
12、06),Liver damage induced by chemotherapy,Sinusoidal lesions,Steatohepatitis,ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY,Vascular Change in Liver Post Systemic Chemotherapy,Clinical significance:impact on surgery,Clinical outcome related to liver damage,Steatosis associated with higher infection rate
13、(Kooby et al, 2003) Steatohepatitis associated with higher mortality rate due to liver failure after surgery (Vauthey et al. 2006) Vascular injury associated with higher rate of operative bleeding and transfusion requirement (Vauthey et al. 2006. Aloia et al. 2006 ),Peroperative chemotherapy: potent
14、ial problems,EORTC 40983:impact of pre-operative chemotherapy on surgery,B O S (Biologics,Oxaliplatin,Surgery) EORTC 40051,Resectable CRC liver metastases: Unanswered Questions,Is peri-operative chemotherapy superior to post-operative chemotherapy? How much preoperative chemotherapy? How do you asse
15、ss nature and extent of chemotherapy-induced liver injury? Do targeted agents modulate chemotherapy-induced liver injury?,Neoadj for unresectable liver metastases of CRC,Chemotherapy for unresectable,Is there a benefit to add surgery to chemotherapy? To which patients? With what regimens? After how
16、much duration of treatment? Take-home message,Chemotherapy for unresectable,Is there a benefit to add surgery to chemotherapy? To which patients? With what regimens? After how much duration of treatment? Take-home message,Downstaging Unresectable Colorectal Metastases,Response to neoadjuvant chemoth
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- 关 键 词:
- 直肠癌 转移 辅助 化疗 共识 争议
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