Skip to main content
SpringerLink
Log in

High Neutrophil Count as a Negative Prognostic Factor for Relapse in Patients with Thymic Epithelial Tumor

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

Abstract

Purpose

Preoperative neutrophil count is reportedly associated with poor prognosis in cancer patients. This study aimed to investigate the clinical significance of pre-treatment peripheral blood cell counts in patients with thymic epithelial tumors (TETs).

Methods

A retrospective review of 71 patients with completely resected TETs [64 thymoma, 6 thymic carcinoma, and 1 thymic neuroendocrine tumor] between 2000 and 2018 was conducted. Associations between tumor recurrence and pre-treatment peripheral blood cell counts of leukocytes (WBC), neutrophils (Neut), lymphocytes (Lymph), monocytes (Mono), and platelets (Plt) were analyzed. Optimal cut-off points were selected using receiver operating characteristic curve analysis to predict tumor recurrence.

Results

High WBC (≥ 7000), Neut (≥ 4450), and Plt (≥ 226 × 103) counts had significantly poor relapse-free survival (RFS), but high Lymph (≥ 1950) and Mono (≥ 400) did not. High Neut had the strongest correlation with recurrence (area under curve, 0.800); we focused on the analysis between high-Neut and low-Neut groups. High Neut count significantly correlated with smoking history, pre-treatment C-reactive protein level, and advanced stage; high Neut count and aggressive histology tended to show correlations. RFS was significantly poorer in the high-Neut group than in the low-Neut group (p = 0.003), with 5-year RFS rates of 63.8% and 96.8%, respectively. High Neut count was a significant adverse predictor for RFS and cumulative incidence of recurrence (p = 0.005 and p < 0.001, respectively). The risk scoring system comprising high Neut count, advanced stage, and aggressive histology demonstrated better prognostic ability than any prognostic factors alone.

Conclusions

High Neut count significantly correlated with TET recurrence, suggesting a negative prognostic effect of latent inflammation in TET patients.

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
Fig. 4

Similar content being viewed by others

References

  1. de Jong WK, Blaauwgeers JL, Schaapveld M, Timens W, Klinkenberg TJ, Groen HJ. Thymic epithelial tumors: a population-based study of the incidence, diagnostic procedures and therapy. Eur J Cancer. 2008; 44:123–30.

    Article  Google Scholar 

  2. Marx A, Chan JK, Coindre JM, et al. The 2015 World Health Organization classification of tumors of the thymus: continuity and changes. J Thorac Oncol. 2015; 10:1383–95.

    Article  CAS  Google Scholar 

  3. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG thymic epithelial tumors staging project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014; 9:S65–72.

    Article  Google Scholar 

  4. Fukui T, Fukumoto K, Okasaka T, et al. Clinical evaluation of a new tumor-node-metastasis staging system for thymic malignancies proposed by the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group. Eur J Cardiothorac Surg. 2016; 49:574–9.

    Article  Google Scholar 

  5. Okumura M, Yoshino I, Yano M, et al. Tumor size determines both recurrence-free survival and disease-specific survival after surgical treatment for thymoma. Eur J Cardiothorac Surg. 2019; 56:174–81.

    Article  Google Scholar 

  6. Detterbeck F, Youssef S, Ruffini E, Okumura M. A review of prognostic factors in thymic malignancies. J Thorac Oncol. 2011; 6:S1698–S1704.

    Article  Google Scholar 

  7. Takahashi Y, Horio H, Hato T, et al. Prognostic significance of preoperative neutrophil-lymphocyte ratios in patients with stage I non-small cell lung cancer after complete resection. Ann Surg Oncol. 2015; 22:S1324–31.

    Article  Google Scholar 

  8. Templeton AJ, McNamara MG, Seruga 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:dju124.

    Article  Google Scholar 

  9. Sionov RV, Fridlender ZG, Granot Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron. 2015; 8:125–58.

    Article  CAS  Google Scholar 

  10. Ocana A, Nieto-Jimenez C, Pandiella A, Templeton AJ. Neutrophils in cancer: prognostic role and therapeutic strategies. Mol Cancer. 2017; 16:137.

    Article  Google Scholar 

  11. Nakajima J, Murakawa T, Fukami T, Sano A, Takamoto S, Ohtsu H. Postthymectomy myasthenia gravis: relationship with thymoma and antiacetylcholine receptor antibody. Ann Thorac Surg. 2008;86:941–45.

    Article  Google Scholar 

  12. Yamada Y, Yoshida S, Iwata T, et al. Risk factors for developing postthymectomy myasthenia gravis in thymoma patients. Ann Thorac Surg. 2015; 99:1013–19.

    Article  Google Scholar 

  13. Moran CA, Weissferdt A, Kalhor N, et al. Thymomas I: a clinicopathologic correlation of 250 cases with emphasis on the World Health Organization schema. Am J Clin Pathol. 2012; 137:444–50.

    Article  Google Scholar 

  14. Strobel P, Bauer A, Puppe B, et al. Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis. J Clin Oncol. 2004; 22:1501–09.

    Article  Google Scholar 

  15. Yanagiya M, Nitadori JI, Nagayama K, Anraku M, Sato M, Nakajima J. Prognostic significance of the preoperative neutrophil-to-lymphocyte ratio for complete resection of thymoma. Surg Today. 2018; 48:422–30.

    Article  Google Scholar 

  16. Janik S, Raunegger T, Hacker P, et al. Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome. Oncotarget. 2018; 9:21861–75.

    Article  Google Scholar 

  17. Janik S, Bekos C, Hacker P, et al. Elevated CRP levels predict poor outcome and tumor recurrence in patients with thymic epithelial tumors: a pro- and retrospective analysis. Oncotarget. 2017; 8:47090–102.

    Article  Google Scholar 

  18. Yuan ZY, Gao SG, Mu JW, et al. Prognostic value of preoperative neutrophil-lymphocyte ratio is superior to platelet-lymphocyte ratio for survival in patients who underwent complete resection of thymic carcinoma. J Thorac Dis. 2016; 8:1487–96.

    Article  Google Scholar 

  19. Muriana P, Carretta A, Ciriaco P, Bandiera A, Negri G. Assessment of the prognostic role of neutrophil-to-lymphocyte ratio following complete resection of thymoma. J Cardiothorac Surg. 2018; 13:119.

    Article  Google Scholar 

  20. Meager A, Wadhwa M, Dilger P, et al. Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Clin Exp Immunol. 2003; 132:128–36.

    Article  CAS  Google Scholar 

  21. Rosales C. Neutrophil: a cell with many roles in inflammation or several cell types? Front Physiol. 2018; 9:113.

    Article  Google Scholar 

  22. Granot Z, Henke E, Comen EA, et al. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011; 20:300–14.

    Article  CAS  Google Scholar 

  23. Inai K, Takagi K, Takimoto N, et al. Multiple inflammatory cytokine-productive ThyL-6 cell line established from a patient with thymic carcinoma. Cancer Sci. 2008; 99:1778–84.

    Article  CAS  Google Scholar 

  24. Teramukai S, Kitano T, Kishida Y, et al. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009; 45:1950–58.

    Article  Google Scholar 

  25. Marulli G, Margaritora S, Lucchi M, et al. Surgical treatment of recurrent thymoma: is it worthwhile? Eur J Cardiothorac Surg. 2016; 49:327–32.

    Article  Google Scholar 

Download references

Acknowledgement

This work was supported by Grant-in-Aid for Scientific Research, Japan Society for the Promotion of Science (JSPS KAKENHI Grant No. J16K10705).

Author information

Authors and Affiliations

  1. Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Satoru Okada MD, PhD, Masanori Shimomura MD, PhD, Hiroaki Tsunezuka MD, PhD, Shunta Ishihara MD, Satoshi Ikebe MD, Tatsuo Furuya MD, Junichi Shimada MD, PhD & Masayoshi Inoue MD, PhD

  2. Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Satoshi Teramukai PhD

Authors
  1. Satoru Okada MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masanori Shimomura MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroaki Tsunezuka MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shunta Ishihara MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Satoshi Ikebe MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tatsuo Furuya MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Junichi Shimada MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Satoshi Teramukai PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masayoshi Inoue MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masayoshi Inoue MD, PhD.

Ethics declarations

Disclosures

Satoru Okada, Masanori Shimomura, Hiroaki Tsunezuka, Shunta Ishihara, Satoshi Ikebe, Tatsuo Furuya, Junichi Shimada, Satoshi Teramukai, and Masayoshi Inoue declare there are no conflicts of interest to disclose.

Additional information

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 97 kb)

Supplementary material 2 (PDF 192 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Okada, S., Shimomura, M., Tsunezuka, H. et al. High Neutrophil Count as a Negative Prognostic Factor for Relapse in Patients with Thymic Epithelial Tumor. Ann Surg Oncol 27, 2438–2447 (2020). https://doi.org/10.1245/s10434-020-08228-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-020-08228-9

Search

Navigation