Skip to main content

Advertisement

Log in

Lymphopenia after induction chemotherapy correlates with incomplete surgical resection in patients with advanced ovarian cancer

International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Lymphopenia is associated with poor outcomes in patients with various cancers, but little is known about the prognostic impact of lymphopenia in patients with epithelial ovarian cancer (EOC) after induction chemotherapy (IC). This study investigated the prognostic significance of pre- and post-IC lymphopenia in patients with advanced EOC.

Methods

We reviewed medical records of 68 patients with stage III/IV ovarian, fallopian tube, or peritoneal cancer treated with IC at our institution between 2009 and 2017. We assessed the associations of pre- and post-IC inflammatory markers, including lymphocyte counts, with several oncological outcomes, such as the implementation of interval debulking surgery (IDS), complete resection, progression-free survival (PFS), and overall survival (OS).

Results

Lymphocyte counts increased significantly post-IC compared with the pre-IC values (P = 0.009). Pre-IC lymphopenia was observed in 27 patients (40%), whereas only 16 patients (24%) displayed lymphopenia post-IC (P = 0.020). Among several inflammatory markers, only post-IC lymphopenia was significantly associated with incomplete resection outcome during IDS (P = 0.012). Moreover, post-IC lymphopenia was significantly associated with poor PFS (log-rank test, P = 0.009), whereas pre-IC lymphopenia was associated with neither PFS nor OS.

Conclusions

Post-IC lymphopenia may predict incomplete resection during IDS and poor prognosis in patients with advanced EOC.

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

Access this article

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. Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30

    Article  PubMed  Google Scholar 

  2. Morgan RJ Jr, Armstrong DK, Alvarez RD et al (2016) Ovarian cancer, version 1.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 14:1134–1163

    Article  Google Scholar 

  3. Auersperg N, Wong AS, Choi KC et al (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22:255–288

    CAS  PubMed  Google Scholar 

  4. Elattar A, Bryant A, Winter-Roach BA et al (2011) Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev 8:CD007565

    Google Scholar 

  5. Bowen RC, Little NAB, Harmer JR et al (2017) Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget 8:32171–32189

    Article  PubMed Central  PubMed  Google Scholar 

  6. Koh CH, Bhoo-Pathy N, Ng KL et al (2015) Utility of pre-treatment neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer 113:150–158

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Kang MH, Go SI, Song HN et al (2014) The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer 111:452–460

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Taguchi S, Nakagawa T, Matsumoto A et al (2015) Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of survival in patients with metastatic urothelial carcinoma: a multi-institutional study. Int J Urol 22:638–643

    Article  PubMed  Google Scholar 

  9. Kim YJ, Lee I, Chung YS et al (2018) Pretreatment neutrophil-to-lymphocyte ratio and its dynamic change during neoadjuvant chemotherapy as poor prognostic factors in advanced ovarian cancer. Obstet Gynecol Sci 61:227–234

    Article  PubMed Central  PubMed  Google Scholar 

  10. Marchetti C, Romito A, Musella A et al (2018) Combined Plasma Fibrinogen and Neutrophil Lymphocyte Ratio in Ovarian Cancer Prognosis May Play a Role? Int J Gynecol Cancer 28:939–944

    Article  PubMed  Google Scholar 

  11. Williams KA, Labidi-Galy SI, Terry KL et al (2014) Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol 132:542–550

    Article  PubMed Central  PubMed  Google Scholar 

  12. Diakos CI, Charles KA, McMillan DC et al (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol 15:493–503

    Article  Google Scholar 

  13. Galon J, Angell HK, Bedognetti D et al (2013) The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity 39:11–26

    Article  CAS  PubMed  Google Scholar 

  14. Gooden MJ, de Bock GH, Leffers N et al (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Tomšová M, Melichar B, Sedláková I et al (2008) Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol 108:415–420

    Article  CAS  PubMed  Google Scholar 

  16. Lo CS, Sanii S, Kroeger DR et al (2017) Neoadjuvant chemotherapy of ovarian cancer results in three patterns of tumor-infiltrating lymphocyte response with distinct implications for immunotherapy. Clin Cancer Res 23:925–934

    Article  CAS  PubMed  Google Scholar 

  17. Pölcher M, Braun M, Friedrichs N et al (2010) Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother 59:909–919

    Article  CAS  PubMed  Google Scholar 

  18. Milne K, Alexander C, Webb JR et al (2012) Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes. J Transl Med 10:33

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Campian JL, Ye X, Brock M et al (2013) Treatment-related lymphopenia in patients with stage III non-small-cell lung cancer. Cancer Investig 31:183–188

    Article  Google Scholar 

  20. Ray-Coquard I, Cropet C, Van Glabbeke M et al (2009) Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res 69:5383–5391

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. d’Engremont C, Vernerey D, Pointet AL et al (2016) Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study. BMC Cancer 16:823

    Article  PubMed Central  PubMed  Google Scholar 

  22. Liu LT, Chen QY, Tang LQ et al (2018) The prognostic value of treatment-related lymphopenia in nasopharyngeal carcinoma patients. Cancer Res Treat 50:19–29

    Article  CAS  PubMed  Google Scholar 

  23. Kou F, Lu Z, Li J et al (2016) Pretreatment lymphopenia is an easily detectable predictive and prognostic marker in patients with metastatic esophagus squamous cell carcinoma receiving first-line chemotherapy. Cancer Med 5:778–786

    Article  PubMed Central  PubMed  Google Scholar 

  24. Grossman SA, Ellsworth S, Campian J et al (2015) Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw 13:1225–1231

    Article  CAS  Google Scholar 

  25. Grossman SA, Ye X, Lesser G et al (2011) Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res 17:5473–5480

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Balmanoukian A, Ye X, Herman J et al (2012) The association between treatment-related lymphopenia and survival in newly diagnosed patients with resected adenocarcinoma of the pancreas. Cancer Investig 30:571–576

    Article  Google Scholar 

  27. Fang P, Jiang W, Davuluri R et al (2018) High lymphocyte count during neoadjuvant chemoradiotherapy is associated with improved pathologic complete response in esophageal cancer. Radiother Oncol 128:584–590

    Article  PubMed  Google Scholar 

  28. Wild AT, Ye X, Ellsworth SG et al (2015) The association between chemoradiation-related lymphopenia and clinical outcomes in patients with locally advanced pancreatic adenocarcinoma. Am J Clin Oncol 38:259–265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Hollowell JG, van Assendelft OW, Gunter EW et al (2005) Hematological and iron-related analytes—reference data for persons aged 1 year and over: United States, 1988–94. Vital Health Stat 11 247:1–156

    Google Scholar 

  30. Bain B, Seed M, Godsland I (1984) Normal values for peripheral blood white cell counts in women of four different ethnic origins. J Clin Pathol 37:188–193

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Onda T, Yoshikawa H, Yasugi T et al (2010) The optimal debulking after neoadjuvant chemotherapy in ovarian cancer: proposal based on interval look during upfront surgery setting treatment. Jpn J Clin Oncol 40:36–41

    Article  PubMed  Google Scholar 

  32. Ghisoni E, Katsaros D, Maggiorotto F et al (2018) A predictive score for optimal cytoreduction at interval debulking surgery in epithelial ovarian cancer: a two-centers experience. J Ovarian Res 11:42

    Article  PubMed Central  PubMed  Google Scholar 

  33. Baek MH, Lee SW, Park JY et al (2017) Preoperative predictive factors for complete cytoreduction and survival outcome in epithelial ovarian, tubal, and peritoneal cancer after neoadjuvant chemotherapy. Int J Gynecol Cancer 27:420–429

    Article  PubMed  Google Scholar 

  34. Zeng J, Yin J, Song X et al (2016) Reduction of CA125 levels during neoadjuvant chemotherapy can predict cytoreduction to no visible residual disease in patients with advanced epithelial ovarian cancer, primary carcinoma of fallopian tube and peritoneal carcinoma. J Cancer 7:2327–2332

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Smith HA, Kang Y (2013) The metastasis-promoting roles of tumor-associated immune cells. J Mol Med (Berl) 91:411–429

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Enago (http://www.enago.jp) for the English language review.

Funding

This study was not supported by any external sources of funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ayumi Taguchi.

Ethics declarations

Conflict of interest

There are no conflicts of interest to declare.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshino, Y., Taguchi, A., Takao, M. et al. Lymphopenia after induction chemotherapy correlates with incomplete surgical resection in patients with advanced ovarian cancer. Int J Clin Oncol 24, 428–436 (2019). https://doi.org/10.1007/s10147-018-1374-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-018-1374-4

Keywords

Navigation