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Combination of Preoperative Plasma Fibrinogen and Neutrophil-to-Lymphocyte Ratio (the F-NLR Score) as a Prognostic Marker of Locally Advanced Rectal Cancer Following Preoperative Chemoradiotherapy

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Abstract

Background

Coagulation and inflammation play important roles in tumor progression. This study aimed to explore the prognostic impact of combined analysis of fibrinogen and neutrophil-to-lymphocyte (NLR) ratio (F-NLR score) in locally advanced rectal cancer (LARC) receiving preoperative chemoradiotherapy (pCRT) and radical surgery.

Method

Totally 317 patients were included. X-tile analysis was used to determine the optimal cutoff values of preoperative fibrinogen and NLR. F-NLR scores were defined as 2 (both high fibrinogen and NLR), 1 (one of these abnormalities), or 0 (neither abnormality). Time-dependent ROC analysis was used to evaluate the predictive accuracy of fibrinogen, NLR, and F-NLR score. Cox regression analysis was performed to evaluate the prognostic impact of the F-NLR score. A predictive nomogram for disease-free survival (DFS) was developed and validated internally.

Results

One hundred and seventeen (36.9%), 156 (49.2%), and 44 (13.9%) patients had F-NLR score of 0, 1, and 2, respectively. Higher F-NLR score was associated with poorly differentiated tumors, deeper tumor invasion, lymph node metastasis, and more advanced pTNM stage (all P < 0.05). The 5-year OS rates in the F-NLR 0, 1, and 2 groups were 93.6%, 87.3%, and 68.4%, respectively (P < 0.001), while the 5-year DFS rates were 91.8%, 76.8%, and 56.1%, respectively (P < 0.001). Cox regression analysis demonstrated that F-NLR score (F-NLR 1, HR = 2.021, P = 0.046; F-NLR 2, HR = 3.356, P = 0.002), pTNM stage III (HR = 3.109, P = 0.009), and circumferential resection margin (CRM) involvement (HR = 3.120, P = 0.021) were independently associated with DFS. A nomogram for DFS was developed (C-index 0.708).

Conclusion

F-NLR score is a promising predictor for disease recurrence in LARC patients after pCRT.

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References

  1. van Gijn W, Marijnen CA, Nagtegaal ID et al (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12:575–582

    Article  Google Scholar 

  2. Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933

    Article  CAS  Google Scholar 

  3. Rodel C, Graeven U, Fietkau R et al (2015) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16:979–989

    Article  Google Scholar 

  4. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  Google Scholar 

  5. Templeton AJ, McNamara MG, Seruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106:u124

    Article  Google Scholar 

  6. Li MX, Liu XM, Zhang XF et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 134:2403–2413

    Article  CAS  Google Scholar 

  7. Falanga A, Marchetti M, Vignoli A (2013) Coagulation and cancer: biological and clinical aspects. J Thromb Haemost 11:223–233

    Article  CAS  Google Scholar 

  8. Wang J, Liu H, Shao N et al (2015) The clinical significance of preoperative plasma fibrinogen level and platelet count in resectable esophageal squamous cell carcinoma. World J Surg Oncol 13:157. https://doi.org/10.1186/s12957-015-0543-4

    Article  PubMed  PubMed Central  Google Scholar 

  9. Huang G, Jiang H, Lin Y et al (2018) Prognostic value of plasma fibrinogen in hepatocellular carcinoma: a meta-analysis. Cancer Manag Res 10:5027–5041

    Article  CAS  Google Scholar 

  10. Zhong H, Qian Y, Fang S et al (2018) Prognostic value of plasma fibrinogen in lung cancer patients: a meta-analysis. J Cancer 9:3904–3911

    Article  CAS  Google Scholar 

  11. Kawai K, Kitayama J, Tsuno NH et al (2011) Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response and poor prognosis in rectal cancer. Int J Colorectal Dis 26:45–51

    Article  Google Scholar 

  12. Lu K, Zhu Y, Sheng L et al (2011) Serum fibrinogen level predicts the therapeutic response and prognosis in patients with locally advanced rectal cancer. Hepatogastroenterology 58:1507–1510

    Article  CAS  Google Scholar 

  13. Arigami T, Uenosono Y, Matsushita D et al (2016) Combined fibrinogen concentration and neutrophil-lymphocyte ratio as a prognostic marker of gastric cancer. Oncol Lett 11:1537–1544

    Article  Google Scholar 

  14. Kijima T, Arigami T, Uchikado Y et al (2017) Combined fibrinogen and neutrophil-lymphocyte ratio as a prognostic marker of advanced esophageal squamous cell carcinoma. Cancer Sci 108:193–199

    Article  CAS  Google Scholar 

  15. Wang H, Zhao J, Zhang M et al (2018) The combination of plasma fibrinogen and neutrophil lymphocyte ratio (F-NLR) is a predictive factor in patients with resectable non small cell lung cancer. J Cell Physiol 233:4216–4224

    Article  CAS  Google Scholar 

  16. Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10:7252–7259

    Article  CAS  Google Scholar 

  17. Zheng S, Shen J, Jiao Y et al (2009) Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci 100:859–865

    Article  CAS  Google Scholar 

  18. Seth R, Tai LH, Falls T et al (2013) Surgical stress promotes the development of cancer metastases by a coagulation-dependent mechanism involving natural killer cells in a murine model. Ann Surg 258:158–168

    Article  Google Scholar 

  19. Perisanidis C, Psyrri A, Cohen EE et al (2015) Prognostic role of pretreatment plasma fibrinogen in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev 41:960–970

    Article  CAS  Google Scholar 

  20. Foley JH, Conway EM (2016) Cross talk pathways between coagulation and inflammation. Circ Res 118:1392–1408

    Article  CAS  Google Scholar 

  21. Steinbrecher KA, Horowitz NA, Blevins EA et al (2010) Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen. Cancer Res 70:2634–2643

    Article  CAS  Google Scholar 

  22. McMillan DC (2013) The systemic inflammation-based glasgow prognostic score: a decade of experience in patients with cancer. Cancer Treat Rev 39:534–540

    Article  Google Scholar 

  23. Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10:9–22

    Article  CAS  Google Scholar 

  24. Roxburgh CS, McMillan DC (2014) Cancer and systemic inflammation: treat the tumour and treat the host. Br J Cancer 110:1409–1412

    Article  CAS  Google Scholar 

  25. Park JH, McMillan DC, Horgan PG et al (2014) The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer. Cancer Treat Rev 40:68–77

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank all the staff in the Department of colorectal surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China.

Funding

This study was supported by Construction Project of Fujian Province Minimally Invasive Medical Center (Grant Number: [2017]171), Startup Fund for Scientific Research, Fujian Medical University (Grant Number: 2017XQ1028), Joint Funds for the Innovation of Science and Technology, Fujian province (Grant Number: 2018Y9030), and Young and Middle-aged Backbone Training Project in the Health System of Fujian province (Grant Number: 2019-ZQN-45).

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Author notes

  1. Yanwu Sun and Yiyi Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, People’s Republic of China

    Yanwu Sun, Yiyi Zhang, Zhekun Huang, Huiming Lin, Xingrong Lu, Ying Huang & Pan Chi

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  1. Yanwu Sun
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  2. Yiyi Zhang
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  3. Zhekun Huang
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  4. Huiming Lin
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  7. Pan Chi
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Correspondence to Pan Chi.

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Sun, Y., Zhang, Y., Huang, Z. et al. Combination of Preoperative Plasma Fibrinogen and Neutrophil-to-Lymphocyte Ratio (the F-NLR Score) as a Prognostic Marker of Locally Advanced Rectal Cancer Following Preoperative Chemoradiotherapy. World J Surg 44, 1975–1984 (2020). https://doi.org/10.1007/s00268-020-05407-3

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  • DOI: https://doi.org/10.1007/s00268-020-05407-3

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