Skip to main content

Advertisement

SpringerLink
Log in

Short Chemotherapy-Free Interval Improves Oncological Outcome in Patients Undergoing Two-Stage Hepatectomy for Colorectal Liver Metastases

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

In patients undergoing two-stage hepatectomy (TSH) for colorectal liver metastases (CRLM), chemotherapy is discontinued before portal vein occlusion and restarted after curative resection. Long chemotherapy-free intervals (CFI) may lead to tumor progression and poor oncological outcomes.

Objective

The aim of this study was to investigate the impact of the length of CFI on oncological outcome in patients undergoing TSH for CRLM.

Patients and Methods

Overall, 74 patients suffering from bilobar CRLM who underwent ALPPS (associating liver partition with portal vein ligation for staged hepatectomy; n = 43) or conventional TSH (n = 31) at two tertiary centers were investigated. The impact of CFI on long-term outcomes was analyzed by univariable and multivariable analysis.

Results

Preoperative chemotherapy was administered in 91 % (67/74) of patients, and chemotherapy was resumed postoperatively in 69 % (44/64) of patients who completed TSH. The use of postoperative chemotherapy was significantly associated with improved mean overall survival (36 ± 3 vs. 13 ± 3 months; p < 0.001). Overall, the median CFI from surgery to postoperative chemotherapy was 16 weeks (interquartile range 11–31) and was significantly shorter in the ALPPS group when compared with the conventional TSH group (10 vs. 21 weeks; p < 0.001). Multivariable analysis revealed a CFI ≤ 10 weeks as an independent factor associated with improved overall survival (p = 0.006) and disease-free survival (p = 0.010).

Conclusion

A short CFI is associated with improved oncological outcome in patients undergoing TSH for CRLM. Decreased interstage intervals after ALPPS may facilitate the timely resumption of chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. 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(9617):1007-16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1208-15.

    Article  CAS  PubMed  Google Scholar 

  3. Lehmann K, Rickenbacher A, Weber A, et al. Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg. 2012;255(2):237-47.

    Article  PubMed  Google Scholar 

  4. Adam R, Laurent A, Azoulay D, et al. Two-stage hepatectomy: a planned strategy to treat irresectable liver tumors. Ann Surg. 2000;232(6):777-85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Clavien PA, Petrowsky H, DeOliveira ML, et al. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007;356(15):1545-59.

    Article  PubMed  Google Scholar 

  6. Zorzi D, Laurent A, Pawlik TM, et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94(3):274-86.

    Article  CAS  PubMed  Google Scholar 

  7. Brouquet A, Belghiti J. Chemotherapy and its effect on liver hypertrophy: implications for portal vein embolization and resection. Semin Intervent Radiol. 2008;25(2):162-7.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Malietzis G, Mughal A, Currie AC, et al. Factors implicated for delay of adjuvant chemotherapy in colorectal cancer: a meta-analysis of observational studies. Ann Surg Oncol. 2015;22(12):3793-802.

    Article  PubMed  Google Scholar 

  9. Des Guetz G, Nicolas P, Perret GY, et al. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer. 2010;46(6):1049-55.

    Article  PubMed  Google Scholar 

  10. Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol. 2011;29(8):1083-1090.

    Article  PubMed  PubMed Central  Google Scholar 

  11. de Santibanes E, Clavien PA. Playing Play-Doh to prevent postoperative liver failure: the “ALPPS” approach. Ann Surg. 2012;255(3):415-7.

    Article  PubMed  Google Scholar 

  12. Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255(3):405-14.

    Article  PubMed  Google Scholar 

  13. Schadde E, Ardiles V, Slankamenac K, et al. ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies: results of a multicenter analysis. World J Surg. 2014;38(6):1510-9.

    Article  PubMed  Google Scholar 

  14. Berglund A, Cedermark B, Glimelius B. Is it deleterious to delay the start of adjuvant chemotherapy in colon cancer stage III? Ann Oncol. 2008;19(2):400-2.

    Article  CAS  PubMed  Google Scholar 

  15. Czaykowski PM, Gill S, Kennecke HF, et al. Adjuvant chemotherapy for stage III colon cancer: does timing matter? Dis Colon Rectum. 2011;54(9):1082-9.

    Article  PubMed  Google Scholar 

  16. Biagi JJ, Raphael MJ, Mackillop WJ, et al. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305(22):2335-42.

    Article  CAS  PubMed  Google Scholar 

  17. Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240(6):1052-61; discussion 1061-4.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Allen PJ, Kemeny N, Jarnagin W, et al. Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. J Gastrointest Surg. 2003;7(1):109-15; discussion 116-7.

    Article  PubMed  Google Scholar 

  19. Adam R, Bhangui P, Poston G, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252(5):774-87.

    Article  PubMed  Google Scholar 

  20. Spelt L, Sparrelid E, Isaksson B, et al. Tumour growth after portal vein embolization with pre-procedural chemotherapy for colorectal liver metastases. HPB (Oxford). 2015;17(6):529-535.

    Article  Google Scholar 

  21. Wicherts DA, Miller R, de Haas RJ, et al. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg. 2008;248(6):994-1005.

    Article  PubMed  Google Scholar 

  22. Pamecha V, Nedjat-Shokouhi B, Gurusamy K, et al. Prospective evaluation of two-stage hepatectomy combined with selective portal vein embolisation and systemic chemotherapy for patients with unresectable bilobar colorectal liver metastases. Dig Surg. 2008;25(5):387-93.

    Article  CAS  PubMed  Google Scholar 

  23. Goere D, Farges O, Leporrier J, et al. Chemotherapy does not impair hypertrophy of the left liver after right portal vein obstruction. J Gastrointest Surg. 2006;10(3):365-70.

    Article  PubMed  Google Scholar 

  24. Beal IK, Anthony S, Papadopoulou A, et al. Portal vein embolisation prior to hepatic resection for colorectal liver metastases and the effects of periprocedure chemotherapy. Br J Radiol. 2006;79(942):473-8.

    Article  CAS  PubMed  Google Scholar 

  25. Oldhafer KJ, Donati M, Jenner RM, et al. ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence. World J Surg. 2014;38(6):1504-9.

    Article  PubMed  Google Scholar 

  26. Abdalla EK, Hicks ME, Vauthey JN. Portal vein embolization: rationale, technique and future prospects. Br J Surg. 2001;88(2):165-75.

    Article  CAS  PubMed  Google Scholar 

  27. Broering DC, Hillert C, Krupski G, et al. Portal vein embolization vs. portal vein ligation for induction of hypertrophy of the future liver remnant. J Gastrointest Surg. 2002;6(6):905-913.

    Article  PubMed  Google Scholar 

  28. Robles R, Marin C, Lopez-Conesa A, et al. Comparative study of right portal vein ligation versus embolisation for induction of hypertrophy in two-stage hepatectomy for multiple bilateral colorectal liver metastases. Eur J Surg Oncol. 2012;38(7):586-593.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Mickael Lesurtel is supported by a professorship Grant from the Swiss National Science Foundation (PP00P3_128475).

Author information

Authors and Affiliations

  1. Department of Visceral and Transplant Surgery, Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland

    P. Kambakamba MD, M. Linecker MD, D. A. Raptis MD, P. Kron MD, H. Petrowsky MD, P. A. Clavien MD, PhD, FACS & M. Lesurtel MD, PhD

  2. Department of General Surgery Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    F. A. Alvarez MD & E. de Santibanes MD, PhD, FACS

  3. Department of Oncology, University Hospital Zurich, Zurich, Switzerland

    P. Samaras MD

  4. Department of Radiology, University Hospital Zurich, Zurich, Switzerland

    C. S. Reiner MD

  5. Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon, Lyon, France

    M. Lesurtel MD, PhD

Authors
  1. P. Kambakamba MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Linecker MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. A. Alvarez MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Samaras MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. S. Reiner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. A. Raptis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Kron MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. de Santibanes MD, PhD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H. Petrowsky MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P. A. Clavien MD, PhD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. Lesurtel MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Lesurtel MD, PhD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 59 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kambakamba, P., Linecker, M., Alvarez, F.A. et al. Short Chemotherapy-Free Interval Improves Oncological Outcome in Patients Undergoing Two-Stage Hepatectomy for Colorectal Liver Metastases. Ann Surg Oncol 23, 3915–3923 (2016). https://doi.org/10.1245/s10434-016-5419-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-016-5419-5

Keywords

Search

Navigation