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Surgical Management of Colorectal Hepatic Metastases

Surgical Management of Colorectal Hepatic Metastases. Elin R. Sigurdson, M.D., Ph.D. Fox Chase Cancer Center ASCO 2006. Colorectal Hepatic Metastases Surgery. Adjuvant Therapy After Liver Resection ECOG Study Design. Liver Resection. Hepatic Arterial Infusion + Systemic (HAI + SYS).

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Surgical Management of Colorectal Hepatic Metastases

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  1. Surgical Management of Colorectal Hepatic Metastases Elin R. Sigurdson, M.D., Ph.D. Fox Chase Cancer Center ASCO 2006

  2. Colorectal Hepatic MetastasesSurgery

  3. Adjuvant Therapy After Liver ResectionECOG Study Design Liver Resection Hepatic Arterial Infusion + Systemic (HAI + SYS) Control

  4. Adjuvant Therapy After Liver ResectionMSKCC Study Design Liver Resection Hepatic Arterial Infusion + Systemic (HAI + SYS) Systemic (SYS)

  5. Updated Overall Survival p=0.10 5 years 10 years Kemeny NE. N Engl J Med 2005;352(7):734-5.

  6. Updated Progression Free Survival p=0.02 Kemeny NE. N Engl J Med 2005;352(7):734-5.

  7. Meta-analysisAdjuvant chemotherapy after liver resection • ENG • Number of mets(1 vs. ≥ 2) • Treatment center • Disease free interval(≤ 6 vs. > 6 months) • Liver vs. lung mets • Prior adjuvant chemo • FFCD • Number of mets(1 vs. ≥ 2) • Maximum size of mets(≤ 5 vs. > 5 cm) • Disease free interval(≤ 1 vs. > 1 year) • Prior adjuvant chemo

  8. Meta-analysis • Progression Free Survival by treatment group

  9. Meta-analysis • Overall survival by treatment group

  10. Colorectal Hepatic MetastasesSurgery vs Surgery + Adjuvant Chemo

  11. Colorectal Hepatic MetastasesSurgery vs Surgery + Adjuvant Chemo

  12. Colorectal Hepatic MetastasesSurgery vs Surgery + Adjuvant Chemo

  13. Colorectal Hepatic MetastasesSurgery vs Surgery + Adjuvant Chemo

  14. ToxicityHAI FUDR/IV 5-FU vs HAI FUDR/IV CapOX

  15. ToxicityHAI FUDR/IV 5-FU vs HAI FUDR/IV CapOX

  16. LiverMetSurvey (retrospective) : 2122 patients with liver resections  Liverpool Villejuif  Zurich   Geneva Torino  

  17. LIVERMETSURVEY: Objectives • To analyze survivals in relation to pertinent prognostic factors • To provide information on a multi-institutional basis on currently pending questions regarding indications, type of surgery, adjuvant treatments, role of chemotherapy, etc.

  18. Colorectal Hepatic MetastasesClinical Risk Score • Node-positive primary cancer • Disease-free interval < 12 months • > 1 tumor • Tumor size > 5 cm • CEA > 200 ng/m Risk factors (1 point each): Fong Y. Ann Surg. 1999. 230:309.

  19. Colorectal Hepatic MetastasesClinical Risk Score Fong Y. Ann Surg. 1999. 230:309.

  20. 100 80 60 Survival (%) 40 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurveyOverall Survivals After Resection (n=1900) 90% 59% 42% 26%

  21. 92% > 3 nodules : 398  3 nodules : 1369 100 85% 64% Log rank p < 0.0001 80 48% 60 31% Survival (%) 42% 40 24% 10% 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurveySurvival by Tumor Number

  22. 100 80 60 Survival (%) 40 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurveySurvival by Extent of Disease 92% Unilateral : 1001 Bilateral : 759 89% 63% Log rank p = 0.0002 47% 56% 33% 38% 19%

  23. 100 80 60 Survival (%) 40 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurveySurvival by Tumor Size 92%  50 mm : 498 < 50 mm : 1023 88% Log rank p = 0.03 60% 45% 56% 29% 38% 22%

  24. 100 80 60 Survival (%) 40 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurveySurvivals by Preop Chemo 90% With Chemo pre hep1 : 825 Without chemo : 676 89% 65% Log rank p = 0.002 50% 56% 26% 38% 25%

  25. Colorectal Hepatic MetastasesClinical Risk Score

  26. Colorectal Hepatic MetastasesClinical Risk Score

  27. A GERCOR StudyPatients and Methods Optimox 1 study design Inclusion criteria Histologically proven colorectal cancer Unresectable metastases No prior CT except adjuvant CT if ended  6 months before study entry WHO PS  2 Adequate hematological, renal and liver functions < 80 years Evaluation after 4, 6 and then every 6 cycles

  28. Optimox 1 SurgeryOverall Survival since R0-R1 surgery

  29. Optimox 1 SurgeryOS according to time to surgery

  30. Colorectal Hepatic MetastasesSurgery vs Surgery + Adjuvant Chemo

  31. Chemotherapy FOLFOX (n=9) CAPOX (n=9) FOLFIRI (n=7) Resection Liver (n=27) Lung (n= 3) Peritoneal (n= 1) Other (n=1) Adding Bevacizumab to Preoperative Chemotherapy for Liver MetastasesFirst Beat-Study

  32. Adding Bevacizumab to Preoperative Chemotherapy for Liver MetastasesFirst Beat-Study • Complications (7/31) • Stomach perforation • Pleural effusion • Wound infection • Portal vein thrombosis/MI • Bowel obstruction • Ascites • Ileus/cornea infection

  33. Resectable Hepatic Metastases • Adjuvant chemotherapy after potentially curative resection: A meta-analysis. • Mitry e, Fields A, Bleiberg H et al. • Adjuvant systemic capecitabine and oxaliplatin administered with HAI FUdR • Alberts SR, Mahoney M, Donohue J, et al.

  34. Preoperative Chemotherapy for Hepatic Metastases • Optimox 1 study. • Perez-Staub N, Lledo G, Paye F et al. • LiverMetSurvey: Efficacy of preop chemotherapy • Adam R, Aloia T, Figueras J et al • First Beat-study • Michael M, Vancutsem E, Kretzschmar A et al

  35. LiverMetSurvey(2,122 patients) • Mortality 1.2% • Median survival 46 months • 5-Year survival 42% • Preoperative chemotherapy did not benefit solitary metastases • PC 45% vs no PC 58% 5YS

  36. Adjuvant Chemotherapy for Solitary Hepatic Metastases Kemeny NE

  37. Factors associated with survival in univariate analysis • Progression Free Survival * FFCD trial, 171 patients Only factors associated with PFS with a p value < 0.1 are presented

  38. 94% With Chemo pre hep1 : 226 Without chemo : 363 100 90% 68% 80 Log rank p = 0.54 58% 60 33% Survival (%) 45% 40 32% 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurvey: Multifactorial AnalysisSurvival by Preop Chemo ANDTumor Number = 1

  39. With Chemo pre hep1 : 139 Without chemo : 22 100 80 60 Survival (%) 40 20 0 1 2 3 4 5 6 7 8 9 10 Years LiverMetSurvey: Multifactorial AnalysisSurvival by Preop Chemo ANDTumor Number ≥ 5 85% 67% Log rank p = 0.07 39% 22% 25% 5% 12%

  40. Five Year SurvivalSurvival by Number of Metastases

  41. Colorectal Hepatic MetastasesLiverMet Survey: Risk Analysis Risk factors analyzed • Age and sex • Primary tumor site • Disease-free interval • Tumor size • Tumor number • Bilaterality of tumor • Preoperative chemotherapy R Adam, Abstract 3521.

  42. Optimox 1 Surgery:DFS according to time to surgery

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