Pathological response of colorectal liver metastases treated after induction treatment.

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Published Apr 5, 2018
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Vol. 95 No. 10 (2017): Issue Oct 2017

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Sana Ben Slama
Dhouha Bacha
Asma Sassi
Aida Khadhar
Rached Bayar
Saadia Bouraoui
Ahlem Lahmar

Abstract

Background: Mortality for colorectal cancer is mainly due to liver metastases, surgical resection remains the curative treatment and use of neoadjuvant therapy improves resectability of metastases. Pathological response is an important prognostic factor. AIM: To evaluate tumor response by Tumor regression grade (TRG) according Rubbia-Brandt et al and correlation with survival. To establish chemotherapy-related liver injury.
Methods: Thrity-eight patients resected for colorectal cancer liver metastases after neoadjuvant chemotherapy were enrolled in this study. Tumor regression grade (TRG) according to Gradding Rubbia-Brandt et al. was evaluated.
Results: Sex ratio was 1.5 with an average age of was 55 years. Twenty-five patients were in stage IV (65.7% of patients with synchronous liver metastases). Overall survival was 62% at 12 months, 42% at 24 months and 21% at 36 months. Thirty-four patients (89.5%) received Oxaliplatin and nine (23.7%) irinotecan. Twenty patients (52.6%) had no histologic response (TRG 4 and 5), nine (23.7%) had a major response (TRG 1 and 2) and nine had a partial response (TRG3). Survival was more important with major pathologic response than with partial response or no response. No statistically significant relation was found between survival and the different types of response. Chemotherapy-related liver injury were present in 21 patients (55.2%). 
Conclusions: Scoring system with three grades are currently recommanded to evaluate pathological response and new histopathological data are proposed. Larger studies are required to validate these items and their utility for therapeutic decisions.

Keywords:

Chemotherapy, Colorectal cancer, Colorectal liver metastasis, Pathological response, Surgery.

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References

  1. Abdalla EK, Vauthey JN, Ellis LM et al. Recurrence and Outcomes Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection/Ablation for Colorectal Liver Metastases. Ann Surg 2004;239:818‑27.
  2. Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD et al. Trends in Long-Term Survival Following Liver Resection for Hepatic Colorectal Metastases. Ann Surg 2002;235:759‑66.
  3. Pawlik TM, Scoggins CR, Zorzi D et al. Effect of Surgical Margin Status on Survival and Site of Recurrence After Hepatic Resection for Colorectal Metastases. Ann Surg 2005;241:715‑24.
  4. Adam R, De Gramont A, Figueras J et al. The Oncosurgery Approach to Managing Liver Metastases from Colorectal Cancer: A Multidisciplinary International Consensus. Oncologist 2012;17:1225‑39.
  5. Jemal A, Murray T, Ward E et al. Cancer statistics. CA Cancer J Clin 2005;55:10‑30.
  6. Scheele J, Altendorf-Hofmann A. Resection of colorectal liver metastases. Langenbecks Arch Surg 1999;384:313‑27.
  7. Stangl R. Factors influencing the natural history of colorectal liver metastases. Lancet 1994;343:1405‑10.
  8. Aloia T, Sebagh M, Plasse M et al. Liver Histology and Surgical Outcomes After Preoperative Chemotherapy With Fluorouracil Plus Oxaliplatin in Colorectal Cancer Liver Metastases. J Clin Oncol 2006;24:4983‑90.
  9. Baumgaertner I, Ratziu V, Vaillant JC, Hannoun L, Poynard T, André T. Hepatotoxicity of metastatic colorectal cancer chemotherapy: systematic review. Bull Cancer (Paris). 2010;97:559‑69.
  10. Grothey A, Sargent D. Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol 2005;23:9441‑2.
  11. Nordlinger B, Sorbye H, Glimelius B et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 2008;371:1007‑16.
  12. Rubbia-Brandt L, Giostra E, Brezault C et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol 2007;18:299‑304.
  13. Blazer DG, Kishi Y, Maru DM et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 2008;26:5344‑51.
  14. Adam R, Wicherts DA, de Haas RJ et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol 2008;26:1635‑41.
  15. Kleiner DE, Brunt EM, Van Natta M et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313-21.
  16. Rubbia-Brandt L, Lauwers GY, Wang H et al. Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis. Histopathology 2010;56:430-9.
  17. de Haas RJ, Wicherts DA, Flores E, Azoulay D, Castaing D, Adam R. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg 2008;248:626-37.
  18. Kokudo N, Miki Y, Sugai S et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg 2002;137:833-40.
  19. Adam R, Wicherts DA, de Haas RJ et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol 2009;27:1829-35.
  20. Chan G, Hassanain M, Chaudhury P et al. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. HPB (Oxford) 2010;12:277-84.
  21. Abengózar M, Fernández-Aceñero MJ, Chaves S, Celdrán A. Prognostic utility of tumor thickness at the tumor-normal interface in chemotherapy-treated hepatic colorectal metastasis. Pathol Res Pract 2012;208:235-9.
  22. Dede K, Salamon F, Landherr L, Jakab F, Bursics A. Pathologic assessment of response to chemotherapy in colorectal cancer liver metastases after hepatic resection: which method to use? Pathol Oncol Res 2015;21:173-9.
  23. Maru DM, Kopetz S, Boonsirikamchai P et al. Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepa- tic colorectal metastases. Am J Surg Pathol 2010;34:1287-94.
  24. Mentha G, Terraz S, Morel P et al. Dangerous halo after neo-adjuvant chemotherapy and two- step hepatectomy for colorectal liver metastases. Br J Surg 2009;96:95-103.
  25. Falcone A, Masi G, Allegrini G et al. Biweekly chemotherapy with oxaliplatin, irinotecan, infusional Fluorouracil, and leucovorin: a pilot study in patients with metastatic colorectal cancer. J Clin Oncol 2002;20:4006-14.
  26. Seium Y, Stupp R, Ruhstaller T et al. Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study. Ann Oncol 2005;16:762-6.
  27. Vauthey JN, Pawlik TM, Ribero D et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006;24:2065-72.
  28. Rubbia-Brandt L, Audard V, Sartoretti P et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15:460-6.
  29. Karoui M, Penna C, Amin-Hashem M et al. Influence of chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg 2006;243:1-7.
  30. Ribero D, Wang H, Donadon M et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 2007;110:2761-7.
  31. Bibeau F, Rivière B, Boissière F et al. Prise en charge des métastases hépatiques d'origine colorectale après traitement d'induction. Place du pathologiste en 2011. Ann Pathol 2011;31:427-32.
  32. Gómez Dorronsoro ML, Vera R, Ortega L et al. Recommendations of a group of experts for the pathological assessment of tumour regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant therapy. Clin Transl Oncol 2014;16:234-42.