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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-Exclude
5、 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 neoadjuvant
6、CT,Risk that metastases become unresectable if they progress during chemotherapyUncertainty about how to deal with “complete response” to chemotherapyLiver damage induced by chemotherapy,Preoperative chemotherapy: potential problems,Lost window of opportunityTumor growth in a critical area may rende
7、r metastases unresectableChemotherapy 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, anginaRisk factors for developing ATE Age 65 y (P=0.01) Prior history
8、of ATE (P 4.5 cm Residual tumor identified: 83%Chemotherapy reduces sensitivity of PETdetection of matastases2,3Benoist S, et al, J Clin Oncol 24:3939,2006 Akhurst T,et al, J Clin Oncol 23:8713, 2005 Tan, MCB et al, J Gastrointest Surg 11:1112, 2007,“Complete response”:does it cure?,Complete respons
9、e,Preoperative chemotherapy: potential problems,Radiographic CR Pathologoc CRRadiographic CR Pathologoc CR1Resection strategy must remove these lesions“Blind” removal sounds easy in conceptBenoist S, et al, JCO 24:3939, 2006,Chemotherapy induces liver damage The “blue” liver,The type of liver injury
10、 depends on drug administeredVascular lesions: Oxaliplatin(Rubbia-Brandt et al, 2004)Steatosis: 5FU, Irinotecan?(Parikh et al, 2003)Steatohepatitis: Irinotecan(Vauthey et al, 2006),Liver damage induced by chemotherapy,Sinusoidal lesions,Steatohepatitis,ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY,Vasc
11、ular Change in Liver Post Systemic Chemotherapy,Clinical significance:impact on surgery,Clinical outcome related to liver damage,Steatosis associated with higher infection rate (Kooby et al, 2003) Steatohepatitis associated with higher mortality rate due to liver failure after surgery (Vauthey et al
12、. 2006) Vascular injury associated with higher rate of operative bleeding and transfusion requirement(Vauthey et al. 2006. Aloia et al. 2006 ),Peroperative chemotherapy: potential problems,EORTC 40983:impact of pre-operative chemotherapy on surgery,B O S (Biologics,Oxaliplatin,Surgery) EORTC 40051,R
13、esectable CRC liver metastases: Unanswered Questions,Is peri-operative chemotherapy superior to post-operative chemotherapy?How much preoperative chemotherapy?How do you assess nature and extent of chemotherapy-induced liver injury?Do targeted agents modulate chemotherapy-induced liver injury?,Neoad
14、j 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 much duration of treatment? Take-home message,Chemotherapy for unresectable,Is there a benefit to add surgery to chemotherapy?
15、To which patients? With what regimens? After how much duration of treatment? Take-home message,Downstaging Unresectable Colorectal Metastases,Response to neoadjuvant chemothrapy,Survival after liver Resection of Non Resectable Colorectal Matastases after Systemic Chemotherapy,Survival after liver Resection of Colorectal Matastases,
