Skip to main content

Advertisement

SpringerLink
Log in

Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases

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

Abstract

Background

Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in patients with CRLM has not been thoroughly investigated. This original, retrospective study assessed the relationship between the preoperative NLR, survival outcomes, and recurrence patterns in patients after colorectal liver metastasis resection (CRLM).

Methods

The prospectively maintained database of a tertiary medical center was queried for all patients who underwent CRLM resection between 2005 and 2017. Patients were divided into two groups: NLR <3 (normal) or >3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses.

Results

The cohort included 231 patients of whom 53 (23%) had a high neutrophil-to-lymphocyte ratio. At presentation, 35% had synchronous disease and 48% had a solitary metastasis; median tumor size was 2 cm. Patients with a high NLR had a significantly higher rate of simultaneous colorectal resection (P = 0.01). A high NLR was independently associated with worse OS (P = 0.02), worse DFS (P = 0.03), and higher risk of recurrence (P = 0.048), specifically recurrence with an extrahepatic pattern (P = 0.03).

Conclusions

A high preoperative NLR was independently associated with poorer survival outcomes and extrahepatic recurrence pattern. The NLR appears to have prognostic importance in CRLM and may serve as a surrogate marker of aggressive systemic disease after resection. These findings warrant external validation, preferably in a prospective design.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kow AWC. Hepatic metastasis from colorectal cancer. J Gastrointest Oncol. 2019;10(6):1274–98.

    Article  Google Scholar 

  2. Brouquet A, Zimmitti G, Kopetz S, et al. Multicenter validation study of pathologic response and tumor thickness at the tumor-normal liver interface as independent predictors of disease-free survival after preoperative chemotherapy and surgery for colorectal liver metastases. Cancer. 2013;119(15):2778–88.

    Article  Google Scholar 

  3. Adam R, Frilling A, Elias D, et al. Liver resection of colorectal metastases in elderly patients. Br J Surg. 2010;97(3):366–76.

    Article  CAS  Google Scholar 

  4. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.

    Article  Google Scholar 

  5. Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27(22):3677–83.

    Article  Google Scholar 

  6. Poston GJ, Figueras J, Giuliante F, et al. Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol. 2008;26(29):4828–33.

    Article  Google Scholar 

  7. Puppa G, Sonzogni A, Colombari R, Pelosi G. TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med. 2010;134(6):837–52.

    Article  Google Scholar 

  8. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–18; discussion 318–21.

  9. Balachandran VP, Arora A, Gönen M, et al. A validated prognostic multigene expression assay for overall survival in resected colorectal cancer liver metastases. Clin Cancer Res. 2016;22(10):2575–82.

    Article  CAS  Google Scholar 

  10. Kingham TP, Nguyen HCB, Zheng J, et al. MicroRNA-203 predicts human survival after resection of colorectal liver metastasis. Oncotarget. 2017;8(12):18821–31.

    Article  Google Scholar 

  11. Bindea G, Mlecnik B, Tosolini M, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39(4):782–95.

    Article  CAS  Google Scholar 

  12. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.

    Article  CAS  Google Scholar 

  13. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  Google Scholar 

  14. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48(4):526–35.

    Article  CAS  Google Scholar 

  15. McMillan DC, Canna K, McArdle CS. Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg. 2003;90(2):215–9.

    Article  CAS  Google Scholar 

  16. Proctor MJ, Morrison DS, Talwar D, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study. Br J Cancer. 2011;104(4):726–34.

    Article  CAS  Google Scholar 

  17. Kwon HC, Kim SH, Oh SY, et al. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17(3):216–22.

    Article  CAS  Google Scholar 

  18. Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218–30.

    Article  Google Scholar 

  19. Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6(4):283–7.

    Article  CAS  Google Scholar 

  20. Ropponen KM, Eskelinen MJ, Lipponen PK, Alhava E, Kosma VM. Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol. 1997;182(3):318–24.

    Article  CAS  Google Scholar 

  21. Malietzis G, Giacometti M, Kennedy RH, Athanasiou T, Aziz O, Jenkins JT. The emerging role of neutrophil to lymphocyte ratio in determining colorectal cancer treatment outcomes: a systematic review and meta-analysis. Ann Surg Oncol. 2014;21(12):3938–46.

    Article  Google Scholar 

  22. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124.

    Article  Google Scholar 

  23. Giakoustidis A, Neofytou K, Khan AZ, Mudan S. Neutrophil to lymphocyte ratio predicts pattern of recurrence in patients undergoing liver resection for colorectal liver metastasis and thus the overall survival. J Surg Oncol. 2015;111(4):445–50.

    Article  Google Scholar 

  24. Malietzis G, Giacometti M, Askari A, et al. A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery. Ann Surg. 2014;260(2):287–92.

    Article  Google Scholar 

  25. Kaneko M, Nozawa H, Sasaki K, et al. Elevated neutrophil to lymphocyte ratio predicts poor prognosis in advanced colorectal cancer patients receiving oxaliplatin-based chemotherapy. Oncology. 2012;82(5):261–8.

    Article  CAS  Google Scholar 

  26. Zhang Y, Peng Z, Chen M, et al. Elevated neutrophil to lymphocyte ratio might predict poor prognosis for colorectal liver metastasis after percutaneous radiofrequency ablation. Int J Hyperthermia. 2012;28(2):132–40.

    Article  CAS  Google Scholar 

  27. Tohme S, Sukato D, Chalhoub D, et al. Neutrophil-lymphocyte ratio is a simple and novel biomarker for prediction of survival after radioembolization for metastatic colorectal cancer. Ann Surg Oncol. 2015;22(5):1701–7.

    Article  Google Scholar 

  28. He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol. 2019;5(7):953–60.

    Article  Google Scholar 

  29. Margonis GA, Buettner S, Andreatos N, et al. Association of BRAF mutations with survival and recurrence in surgically treated patients with metastatic colorectal liver cancer. JAMA Surg. 2018;153(7):e180996.

    Article  Google Scholar 

  30. Strasberg SM, Phillips C. Use and dissemination of the brisbane 2000 nomenclature of liver anatomy and resections. Ann Surg. 2013;257(3):377–82.

    Article  Google Scholar 

  31. Carpizo DR, Are C, Jarnagin W, et al. Liver resection for metastatic colorectal cancer in patients with concurrent extrahepatic disease: results in 127 patients treated at a single center. Ann Surg Oncol. 2009;16(8):2138–46.

    Article  Google Scholar 

  32. Sadot E, Groot Koerkamp B, Leal JN, et al. Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg. 2015;262(3):476-85; discussion 483–5.

  33. Satagopan JM, Ben-Porat L, Berwick M, Robson M, Kutler D, Auerbach AD. A note on competing risks in survival data analysis. Br J Cancer. 2004;91(7):1229–35.

    Article  CAS  Google Scholar 

  34. Guo C, So Y. Cause-specific analysis of competing risks using the PHREG procedure. SAS Global Forum. Paper SAS2159-2018.

  35. Dexiang Z, Li R, Ye W, et al. Outcome of patients with colorectal liver metastasis: analysis of 1,613 consecutive cases. Ann Surg Oncol. 2012;19(9):2860–8.

    Article  Google Scholar 

  36. Höppener DJ, Nierop PMH, van Amerongen MJ, et al. The disease-free interval between resection of primary colorectal malignancy and the detection of hepatic metastases predicts disease recurrence but not overall survival. Ann Surg Oncol. 2019;26(9):2812–20.

    Article  Google Scholar 

  37. Halazun KJ, Aldoori A, Malik HZ, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol. 2008;34(1):55–60.

    Article  CAS  Google Scholar 

  38. Neal CP, Cairns V, Jones MJ, et al. Prognostic performance of inflammation-based prognostic indices in patients with resectable colorectal liver metastases. Med Oncol. 2015;32(5):144.

    Article  Google Scholar 

Download references

Acknowledgment

The authors thank Tzipora Shochat (Beilinson Hospital) for the statistical services. They also thank Dr. Itamar Giloba and Dr. Noam Amiel for their help with data collection.

Funding

No funding was procured for this work.

Author information

Author notes

  1. Eden Verter and Yael Berger contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel

    Eden Verter MD, Yael Berger MD, Daniel Benchimol MD, Hanoch Kashtan MD & Eran Sadot MD

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Eden Verter MD, Yael Berger MD, Gali Perl MD, Idit Peretz MD, Ana Tovar MD, Sara Morgenstern MD, Baruch Brenner MD, Daniel Benchimol MD, Hanoch Kashtan MD & Eran Sadot MD

  3. Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel

    Gali Perl MD, Idit Peretz MD & Baruch Brenner MD

  4. Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel

    Ana Tovar MD & Sara Morgenstern MD

Authors
  1. Eden Verter MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yael Berger MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gali Perl MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Idit Peretz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Tovar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sara Morgenstern MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baruch Brenner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daniel Benchimol MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hanoch Kashtan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eran Sadot MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eran Sadot MD.

Ethics declarations

Disclosures

The authors report no conflicts of interest.

Ethics approval and consent to participate

The study was approved by the Rabin Medical Center Institutional Ethics Committee.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verter, E., Berger, Y., Perl, G. et al. Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases. Ann Surg Oncol 28, 4320–4329 (2021). https://doi.org/10.1245/s10434-021-10000-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-021-10000-6

Search

Navigation