Annals of Surgical Oncology

, Volume 22, Issue 6, pp 1925–1932 | Cite as

Comparison of Complete Pathologic Response and Hepatic Injuries Between Hepatic Arterial Infusion and Systemic Administration of Oxaliplatin in Patients with Colorectal Liver Metastases

  • Marc Antoine Allard
  • Mylène Sebagh
  • Gaëlle Baillie
  • Antoinette Lemoine
  • Peggy Dartigues
  • François Faitot
  • Matthieu Faron
  • Valérie Boige
  • Fabrizio Vitadello
  • Eric Vibert
  • Dominique Elias
  • René Adam
  • Diane Goéré
  • Antonio Sa Cunha
Hepatobiliary Tumors

Abstract

Background

Whether hepatic arterial infusion (HAI) of oxaliplatin influences the rates of complete pathologic response (CPR) and severe oxaliplatin-related lesions (SOxL) in patients with colorectal liver metastases (CRLM) is unknown. This study aimed to compare the incidence of CPR and SOxL between systemic (intravenous, IV) and HAI administration.

Methods

All patients with initially unresectable CRLM who had undergone hepatic resection in two expert centers between 2004 and 2010 after at least 6 cycles of oxaliplatin-based chemotherapy administered either via HAI (n = 18) or IV (n = 50) were included. The presence of CPR and SOxL were evaluated by two pathologists. A 1:2 case match using a propensity score was used.

Results

A CPR was observed significantly more often after HAI (33 vs. 10 %, P = 0.03). However, SOxL had occurred more frequently in patients in the HAI group versus the IV group, 66 and 20 %, respectively (P < 0.001). On a well-balanced cohort, HAI was associated with higher chance of CPR (odds ratio 9.33, 95 % confidence interval 1.59–54.7) but also higher risk of SOxL (odds ratio 13.7, 95 % confidence interval 3.08–61.3). A CPR markedly enhanced overall survival (OS) and disease-free survival (median OS of 114 vs. 42 months, P = 0.02; median disease-free survival of 51 vs. 12 months, P = 0.002). Patients with SOxL did not experience different outcome (median OS of 42 vs. 50 months, respectively; P = 0.92)

Conclusions

HAI of oxaliplatin increases the likelihood of a CPR at the cost of a higher incidence of SOxL in patients with initially unresectable CRLM.

Keywords

Overall Survival Propensity Score Oxaliplatin Cetuximab Colorectal Liver Metastasis 

Notes

Acknowledgment

The authors would like to thank Dr. David Malka, who provided the clinical data from the CHOICE study, and Lorna Saint Ange for editing.

Disclosure

The authors declare no conflict of interest.

References

  1. 1.
    Bismuth H, Adam R, Levi F, et al. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 1996;224:509–20.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Mocellin S, Pasquali S, Nitti D. Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer. Cochrane Database Syst Rev. 2009;3:CD007823.Google Scholar
  4. 4.
    Kemeny NE, Melendez FD, Capanu M, et al. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009;27:3465–71.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Ducreux M, Ychou M, Laplanche A, et al. Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol. 2005;23:4881–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Goere D, Deshaies I, de Baere T, et al. Prolonged survival of initially unresectable hepatic colorectal cancer patients treated with hepatic arterial infusion of oxaliplatin followed by radical surgery of metastases. Ann Surg. 2010;251:686–91.CrossRefPubMedGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    Blazer DG 3rd, 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.CrossRefPubMedGoogle Scholar
  9. 9.
    Guthoff I, Lotspeich E, Fester C, et al. Hepatic artery infusion using oxaliplatin in combination with 5-fluorouracil, folinic acid and mitomycin C: oxaliplatin pharmacokinetics and feasibility. Anticancer Res. 2003;23(6D):5203–8.PubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    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.CrossRefPubMedGoogle Scholar
  12. 12.
    Rubbia-Brandt L, Tauzin S, Brezault C, et al. Gene expression profiling provides insights into pathways of oxaliplatin-related sinusoidal obstruction syndrome in humans. Mol Cancer Ther. 2011;10:687–96.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    Wicherts DA, de Haas RJ, Sebagh M, et al. Regenerative nodular hyperplasia of the liver related to chemotherapy: impact on outcome of liver surgery for colorectal metastases. Ann Surg Oncol. 2011;18:659–69.CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Vreuls CP, Van Den Broek MA, Winstanley A, et al. Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastases. Histopathology. 2012;61:314–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Tamandl D, Klinger M, Eipeldauer S, et al. Sinusoidal obstruction syndrome impairs long-term outcome of colorectal liver metastases treated with resection after neoadjuvant chemotherapy. Ann Surg Oncol. 2011;18:421–30.CrossRefPubMedGoogle Scholar
  17. 17.
    Adam R, Delvart V, Pascal G, 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.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: a planned strategy to treat irresectable liver tumors. Ann Surg. 2000;232:777–85.CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Levi F, Boige V, Hebbar M, et al. Final results of first European phase II trial of intravenous cetuximab and hepatic artery infusion of irinotecan, 5-fluorouracil, and oxaliplatin in patients with unresectable liver metastases from wt KRAS colorectal cancer after systemic treatment failure (OPTILIV, NCT00852228) [abstract 466]. J Clin Oncol. 2013;31(suppl 4).Google Scholar
  20. 20.
    Deschamps F, Rao P, Teriitehau C, et al. Percutaneous femoral implantation of an arterial port catheter for intraarterial chemotherapy: feasibility and predictive factors of long-term functionality. J Vasc Interv Radiol. 2010;21:1681–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Honore C, Goere D, Dumont F, Elias D. Catheter placement for intra-arterial hepatic chemotherapy. J Visc Surg. 2012;149:389–94.CrossRefPubMedGoogle Scholar
  22. 22.
    Malka DEP, Caramella C, Boucher E, et al. Hepatic arterial infusion (HAI) of oxaliplatin plus intravenous (iv) fluorouracil (FU), leucovorin (LV), and cetuximab for first-line treatment of unresectable colorectal liver metastases (CRLM) (CHOICE): a multicenter phase II study. J Clin Oncol. 2010;28(15 suppl):3558.Google Scholar
  23. 23.
    Colucci G, Gebbia V, Paoletti G, et al. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol. 2005;23:4866–75.CrossRefPubMedGoogle Scholar
  24. 24.
    Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.CrossRefPubMedGoogle Scholar
  25. 25.
    Imamura H, Sano K, Sugawara Y, Kokudo N, Makuuchi M. Assessment of hepatic reserve for indication of hepatic resection: decision tree incorporating indocyanine green test. J Hepatobiliary Pancreat Surg. 2005;12:16–22.CrossRefPubMedGoogle Scholar
  26. 26.
    Soubrane O, Brouquet A, Zalinski S, et al. Predicting high grade lesions of sinusoidal obstruction syndrome related to oxaliplatin-based chemotherapy for colorectal liver metastases: correlation with post-hepatectomy outcome. Ann Surg. 2010;251:454–60.CrossRefPubMedGoogle Scholar
  27. 27.
    Elias D, Lasser P, Rougier P, Ducreux M, Bognel C, Roche A. Frequency, technical aspects, results, and indications of major hepatectomy after prolonged intra-arterial hepatic chemotherapy for initially unresectable hepatic tumors. J Am Coll Surg. 1995;180:213–9.PubMedGoogle Scholar
  28. 28.
    Bismuth H. [Anatomy of the liver and hepatectomy techniques]. Ann Chir. 1998;52:61–3.PubMedGoogle Scholar
  29. 29.
    Balzan S, Belghiti J, Farges O, et al. The “50–50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242:824–8.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Kemeny NE. The re-birth of hepatic arterial infusion for colorectal liver metastases. J Gastrointest Oncol. 2013;4:118–20.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Vigano L, Capussotti L, De Rosa G, De Saussure WO, Mentha G, Rubbia-Brandt L. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. Ann Surg. 2013;258:731–40.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Nakano H, Oussoultzoglou E, Rosso E, et al. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg. 2008;247:118–24.CrossRefPubMedGoogle Scholar
  34. 34.
    Narita M, Oussoultzoglou E, Chenard MP, et al. Liver injury due to chemotherapy-induced sinusoidal obstruction syndrome is associated with sinusoidal capillarization. Ann Surg Oncol. 2012;19:2230–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Makowiec F, Mohrle S, Neeff H, et al. Chemotherapy, liver injury, and postoperative complications in colorectal liver metastases. J Gastrointest Surg. 2011;15:153–64.CrossRefPubMedGoogle Scholar
  36. 36.
    Ryan P, Nanji S, Pollett A, et al. Chemotherapy-induced liver injury in metastatic colorectal cancer: semiquantitative histologic analysis of 334 resected liver specimens shows that vascular injury but not steatohepatitis is associated with preoperative chemotherapy. Am J Surg Pathol. 2010;34:784–91.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Marc Antoine Allard
    • 1
    • 8
  • Mylène Sebagh
    • 2
    • 9
  • Gaëlle Baillie
    • 4
  • Antoinette Lemoine
    • 3
    • 8
  • Peggy Dartigues
    • 6
  • François Faitot
    • 4
  • Matthieu Faron
    • 4
  • Valérie Boige
    • 5
  • Fabrizio Vitadello
    • 4
  • Eric Vibert
    • 1
    • 9
  • Dominique Elias
    • 4
  • René Adam
    • 1
    • 7
  • Diane Goéré
    • 4
  • Antonio Sa Cunha
    • 1
    • 7
  1. 1.Centre Hépato-biliairePaul Brousse HospitalVillejuif CedexFrance
  2. 2.Department of PathologyPaul Brousse HospitalVillejuif CedexFrance
  3. 3.Department of Molecular BiologyPaul Brousse HospitalVillejuif CedexFrance
  4. 4.Department of Surgical OncologyGustave RoussyVillejuif CedexFrance
  5. 5.Department of Medical OncologyGustave RoussyVillejuif CedexFrance
  6. 6.Department of PathologyGustave RoussyVillejuif CedexFrance
  7. 7.Unité INSERM 776, Hôpital Paul BrousseVillejuif CedexFrance
  8. 8.Unité INSERM 1004, Hôpital Paul BrousseVillejuif CedexFrance
  9. 9.Unité INSERM 785, Hôpital Paul BrousseVillejuif CedexFrance

Personalised recommendations