Annals of Surgical Oncology

, Volume 17, Issue 10, pp 2714–2719 | Cite as

Neoadjuvant Chemotherapy in Patients with Stage IV Colorectal Cancer: A Comparison of Histological Response in Liver Metastases, Primary Tumors, and Regional Lymph Nodes

  • Pascal Gervaz
  • Laura Rubbia-Brandt
  • Axel Andres
  • Pietro Majno
  • Arnaud Roth
  • Philippe Morel
  • Gilles Mentha
Gastrointestinal Oncology

Abstract

Background

We report the histopathological results of a novel “inversed” strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes.

Methods

Twenty-nine patients with stage IV CRC received a combination of oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (OCFL) for 3–4 months. Histological response to chemotherapy was assessed by using a tumor regression grading (TRG) score based on presence of residual tumor cells and extent of fibrosis.

Results

Median age of patients was 56 (range, 37–69) years. Primary tumor location was right colon (n = 5), left colon (n = 7), and rectum (n = 17 patients). TRG scores correlated across disease sites (Spearman correlation coefficients for TRG in the primary tumor and lymph nodes was 0.59 [P = 0.005]; for the primary tumor and metastases 0.44 [P = 0.021]; and for lymph nodes and metastases 0.58 [P = 0.006]). Complete absence or poor tumor response (TRG4/5) was significantly more frequent in primary tumors (35.7%) and locoregional lymph nodes (38%) than in liver metastases (6.9%; McNemar test, P = 0.02). Two patients had a complete pathologic response (pT0N0M0).

Conclusions

In patients with stage IV colorectal cancer, liver metastases exhibit a better histological response than primary tumors to OCFL neoadjuvant chemotherapy.

Keywords

Liver Metastasis Irinotecan Oxaliplatin Liver Resection Complete Pathologic Response 

References

  1. 1.
    Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352:476–87.CrossRefPubMedGoogle Scholar
  2. 2.
    Mentha G, Majno PE, Andres A, Rubbia-Brandt L, Morel P, Roth AD. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006;93:872–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Karoui M, Koubaa W, Delbaldo C, Charachon A, Laurent A, Piedbois P, Cherqui D, Tran Van Nhieu J. Chemotherapy has also an effect on primary tumor in colon carcinoma. Ann Surg Oncol. 2008,15:3440–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Mentha G, Majno P, Terraz S, Rubbia-Brandt L, Gervaz P, Andres A, Allal S, et al. Treatment strategies for the management of advanced colorectal liver metastases detected synchronously with the primary tumour. Eur J Surg Oncol. 2007;33(Suppl 2):S76–83.PubMedGoogle Scholar
  5. 5.
    Seium Y, Stupp R, Ruhstaller T, Gervaz P, Mentha G, Philippe M, Allal A, 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Bertheau P, Lerebours F, Mounier N, de Roquancourt A, Espié M, Clot P, Servant JM, et al. Prognostic significance of a combined clinicopathologic score for response to primary systemic therapy in locally advanced breast cancer. Oncol Rep. 2005;14:513–20.PubMedGoogle Scholar
  7. 7.
    Bramwell VH. The role of chemotherapy in the management of non-metastatic operable extremity osteosarcoma. Semin Oncol. 1997;24:561–71.PubMedGoogle Scholar
  8. 8.
    Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard D, Sartoretti P, 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.CrossRefPubMedGoogle Scholar
  9. 9.
    Blazer DG, Kishi Y, Maru DM, Kopetz S, Chun YS, Overman MJ, Fogelman D, et al. Pathologic response to preoperative chemotherapy: a new outcome endpoint after resection of hepatic colorectal metastases. J Clin Oncol. 2008;25:5344–51.CrossRefGoogle Scholar
  10. 10.
    Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.CrossRefPubMedGoogle Scholar
  11. 11.
    Talmadge JE. Clonal selection of metastasis within the life history of a tumor. Cancer Res. 2007;67:11471–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell. 2006;127:679–95.CrossRefPubMedGoogle Scholar
  13. 13.
    Gervaz P, Scholl B, Padrun V, Gillet M. Growth inhibition of liver metastases by the anti-angiogenic drug TNP-470. Liver. 2000;20:108–13.CrossRefPubMedGoogle Scholar
  14. 14.
    Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer. 2002;94:1121–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Vecchio FM, Valentini V, Minsky BD, Padula GD, Venkatraman ES, Balducci M, Micchichè F, et al. The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys. 2005;62:752–60.PubMedGoogle Scholar
  17. 17.
    Mentha G, Roth AD, Terraz S, Giostra E, Gervaz P, Andres A, Morel P, et al. Liver first approach in the treatment of colorectal cancer with synchronous liver metastases. Dig Surg. 2008;25:430–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Leonard GD, Brenner B, Kemeny NE. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2005;23:2038–48.CrossRefPubMedGoogle Scholar
  19. 19.
    Suarez J, Vera R, Balen E, Gomez M, Arias F, Lera JM, Herrera J, Zazpe C. Pathologic response assessed by Mandard grade is a better prognostic factor than down staging for disease-free survival after preoperative radiochemotherapy for advanced rectal cancer. Colorectal Dis. 2008;10:563–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Rubbia-Brandt L, Mentha G, Terris B. Sinusoidal obstruction syndrome is a major feature of hepatic lesions associated with oxaliplatin neoadjuvant chemotherapy for liver colorectal metastases. J Am Coll Surg. 2006;202:199–200.CrossRefPubMedGoogle Scholar
  21. 21.
    Morris-Stiff G, Tan YM, Vauthey JN. Hepatic complications following preoperative chemotherapy with oxaliplatin or irinotecan for hepatic colorectal metastases. Eur J Surg Oncol. 2008;34:609–14.PubMedGoogle Scholar
  22. 22.
    Gervaz P, Scholl B, Mainguene C, Poitry S, Gillet M, Wexner S. Angiogenesis of liver metastases: role of sinusoidal endothelial cells. Dis Colon Rectum.Google Scholar
  23. 23.
    Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer. 2005;5:516–25.CrossRefPubMedGoogle Scholar
  24. 24.
    Mentha G, Terraz S, Morel P, Andres A, Giostra E, Roth A, Rubbia-Brandt L, Majno P. Dangerous halo after neoadjuvant chemotherapy and two-step hepatectomy for colorectal liver metastases. Br J Surg. 2008;96:95–103.CrossRefGoogle Scholar
  25. 25.
    Gervaz P, Morel P. T0N1 adenocarcinoma of the colon following oxaliplatin-based neoadjuvant chemotherapy. J Surg Oncol. 2008.Google Scholar
  26. 26.
    Hughes R, Glynne-Jones R, Grainger J, Richman P, Makris A, Harrison M, Ashford R, et al. Can pathological complete response of the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision? Int J Colorectal Dis. 2006;21:11–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Bedrosian I, Rodriguez-Bigas MA, Feig B, Hunt KK, Ellis L, Curley SA, Vauthey JN, et al. Predicting the node-negative mesorectum after preoperative chemoradiation for locally advanced rectal carcinoma. J Gastrointest Surg. 2004;8:56–62.CrossRefPubMedGoogle Scholar
  28. 28.
    Adam R, Wicherts DA, de Haas RJ, Aloia T, Levi F, Paule B, Guettier C, et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol. 2008;26:1635–41.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Pascal Gervaz
    • 1
  • Laura Rubbia-Brandt
    • 3
  • Axel Andres
    • 1
  • Pietro Majno
    • 1
    • 4
  • Arnaud Roth
    • 2
  • Philippe Morel
    • 1
  • Gilles Mentha
    • 1
    • 4
  1. 1.Department of SurgeryUniversity Hospital GenevaGenevaSwitzerland
  2. 2.Department of OncologyUniversity Hospital GenevaGenevaSwitzerland
  3. 3.Department of PathologyUniversity Hospital GenevaGenevaSwitzerland
  4. 4.Service de Chirurgie Viscérale et TransplantationHôpital Universitaire de GenèveGenevaSwitzerland

Personalised recommendations