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Reporter: R4 李育庭 Supervisor: 鄧豪偉醫師

Pathologic Response to Preoperative Chemotherapy in Colorectal Liver Metastases: Fibrosis, not Necrosis, Predicts Outcome Ann Surg Oncol (2012) 19:2797–2804 Aleksey V. George A. Poultsides , Fei Bao , Elliot L. Servais et al. Reporter: R4 李育庭 Supervisor: 鄧豪偉醫師. Introduction

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Reporter: R4 李育庭 Supervisor: 鄧豪偉醫師

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  1. Pathologic Response to Preoperative Chemotherapy in ColorectalLiver Metastases: Fibrosis, not Necrosis, Predicts OutcomeAnn Surg Oncol (2012) 19:2797–2804Aleksey V. George A. Poultsides, FeiBao, Elliot L. Servaiset al. Reporter: R4 李育庭 Supervisor: 鄧豪偉醫師

  2. Introduction • Patient and Method • Result • Discussion • Conclusion

  3. Introduction

  4. Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Nordlinger B, Sorbye H, Glimelius B, et al. Lancet. Mar 22 2008;371(9617):1007-1016.

  5. Nordlinger B, Sorbye H, Glimelius B, et al. Lancet. Mar 22 2008;371(9617):1007-1016.

  6. Systemic chemotherapy has been shown to convert initially unresectable tumors to resectable.

  7. Adam R, Delvart V, Pascal G, et al. Annals of surgery 2004;240:644-57.

  8. Pathologic response predicts survival after preoperative chemotherapy and resection of CLM (Colorectal liver metastasis).

  9. Blazer DG, 3rd, Kishi Y, Maru DM, et al. J ClinOncol 26:5344-51, 2008

  10. Adam R, Wicherts DA, de Haas RJ, et al. J ClinOncol 26:1635-41, 2008

  11. Rubbia-Brandt L, Giostra E, Brezault C, et al. Ann Oncol 18:299-304, 2007

  12. The pathologic response to neoadjuvant therapy in primary colorectal cancer is not homogeneous. • Fibrosis • Necrosis • Acellular mucin Rubbia-Brandt L, Giostra E, Brezault C, et al. Ann Oncol 18:299-304, 2007

  13. Purpose To evaluate the prevalence of the three components of pathologic response (necrosis, fibrosis, acellularmucin) after resection of CLM, with and without preoperative chemotherapy. To investigate the association with outcome as well as preoperative factors

  14. Patient and Methods

  15. A single institution Retrospective review

  16. Patient Preoperative chemotherapy : Systemic chemotherapy within 6 months before hepatectomy Hepatic artery infusion Non Preoperative chemotherapy Chemotherapy-naive patients chemotherapy-free interval of more than 6 months before hepatectomy Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012

  17. Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012

  18. A median of 3 slides (range, 1–17) were examined for each tumor, typically one section per centimeter of tumor diameter. All tumors that grossly appeared to show complete or near complete response.

  19. Result

  20. Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012

  21. Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012

  22. Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012 Of 21 complete pathologic responders, all but one had received preoperative chemotherapy. 5-year survival probability: 94%

  23. Preoperative chemotherapy Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012

  24. Preoperative chemotherapy Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012

  25. Non Preoperative chemotherapy Only 9 (8 %) and 3 (3 %) of the 117 nonchemotherapy patients had ≥75 % nonviable tumor and fibrosis ≥ 40 %. Lack of association with disease-specific survival

  26. Discussion

  27. Fibrosisis the predominant chemotherapy-induced pathologic change in CLM. Necrosis in CLM is more related to spontaneous phenomena. Thebeneficial effects of chemotherapy appear to be mainly related to the replacement of tumor by fibrosis

  28. The study is the first to provide a detailed quantitative analysis of the three components of overall pathologic response (fibrosis, necrosis, acellularmucin) Fibrosisas the main chemotherapy-induced pathologic change independently associated with survival after resection of CLM.

  29. 8 % were found to have a complete absence of viable tumor cells on pathologic review In the study, patients with complete pathologic response had a 94 % 5-year disease-specific survival probability.

  30. It is important to identify patient or tumor characteristics that preoperatively predict higher levels of pathologic response.

  31. Bevacizumab + Oxaliplatin based chemotherapy Ribero D, Wang H, Donadon M, et al. Cancer 110:2761-7, 2007

  32. Bevacizumab + Oxaliplatin based chemotherapy Blazer DG, 3rd, Kishi Y, Maru DM, et al. J ClinOncol 26:5344-51, 2008

  33. Bevacizumab + Oxaliplatin based chemotherapy Klinger M, Tamandl D, Eipeldauer S, et al. Ann SurgOncol 17:2059-65, 2010

  34. Duration of chemotherapy Poultsides GA, Bao F, Servais EL, et al. Ann SurgOncol 19:2797-804, 2012 Longer duration of preoperative chemotherapy was not associated with pathological response

  35. Duration of chemotherapy Kishi Y, Zorzi D, Contreras CM, et al.AnnSurgOncol 17:2870-6, 2010

  36. Conclusion

  37. Approximately 8 % of patients with CLM receiving modern combination chemotherapy can achieve complete pathologic response. Favorable overall pathologic response is associated with improved long-term survival. The pathologic finding of necrosis in CLM is a nonspecific finding.

  38. HAI chemotherapy and bevacizumab may be associated with higher rates of overall pathologic response and fibrosis.

  39. Thanks for your attention

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