Skip to main content
SpringerLink
Log in

Radiation-related lymphopenia as a new prognostic factor in limited-stage small cell lung cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

The purpose of this study was to investigate whether the minimum absolute lymphocyte count during radiotherapy (min ALC) and the absolute lymphocyte count 1 month after radiotherapy (post ALC) could predict clinical outcome in limited-stage small cell lung cancer (LS-SCLC) patients. We analyzed 73 LS-SCLC patients treated with chemotherapy and radiotherapy; we collected data on the min ALC from 62 patients and on the post ALC from 60 patients. Both min ALC and post ALC were statistically significant predictors of overall survival in multivariate analysis (hazard ratio [95 % confidence interval] 2.67 [1.06–6.75], P = 0.038 and 2.62 [1.19–5.74], P = 0.016, respectively). The median overall survival of the patients with min ALC ≤297 and >297 cells/μL was 12.2 and 35.3 months, respectively (P < 0.001). Patients with post ALC ≤698 and >698 cells/μL had an overall survival of 19.3 and 46.9 months, respectively (P = 0.001). The median overall survival of the lymphopenia (min ALC ≤ 297 cells/μL or post ALC ≤ 698 cells/μL) and the non-lymphopenia group (min ALC > 297 cells/μL and post ALC > 698 cells/μL) was 19.0 and 131.7 months, respectively, while the median progression survival was 8.1 and 16.6 months, respectively (P < 0.001 and P = 0.001). Radiation-related lymphopenia could predict poor survival in LS-SCLC. Its prognostic role should be evaluated in further prospective studies.

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

Similar content being viewed by others

Abbreviations

Min ALC:

Minimum absolute lymphocyte count during radiotherapy

Post ALC:

The absolute lymphocyte count 1 month after radiotherapy

RRL:

Radiation-related lymphopenia

References

  1. Sculier JP, Chansky K, Crowley JJ, Van Meerbeeck J, Goldstraw P, International Staging C, et al. The impact of additional prognostic factors on survival and their relationship with the anatomical extent of disease expressed by the 6th edition of the tnm classification of malignant tumors and the proposals for the 7th edition. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. 2008;3:457–66.

    Google Scholar 

  2. Argiris A, Murren JR. Staging and clinical prognostic factors for small-cell lung cancer. Cancer J. 2001;7:437–47.

    CAS  PubMed  Google Scholar 

  3. Hermes A, Gatzemeier U, Waschki B, Reck M. Lactate dehydrogenase as prognostic factor in limited and extensive disease stage small cell lung cancer—a retrospective single institution analysis. Respir Med. 2010;104:1937–42.

    Article  PubMed  Google Scholar 

  4. Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69:5383–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, 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  PubMed  Google Scholar 

  6. Kang MH, Go SI, Song HN, Lee A, Kim SH, Kang JH, et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer. 2014;111:452–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman J, Pecorelli S, et al. Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix. Int J Radiat Oncol Biol Phys. 2000;48:997–1006.

    Article  CAS  PubMed  Google Scholar 

  8. Lissoni P, Meregalli S, Bonetto E, Mancuso M, Brivio F, Colciago M, et al. Radiotherapy-induced lymphocytopenia: changes in total lymphocyte count and in lymphocyte subpopulations under pelvic irradiation in gynecologic neoplasms. J Biol Regul Homeost Agents. 2005;19:153–8.

    CAS  PubMed  Google Scholar 

  9. Campian JL, Ye X, Brock M, Grossman SA. Treatment-related lymphopenia in patients with stage III non-small-cell lung cancer. Cancer Investig. 2013;31:183–8.

    Article  Google Scholar 

  10. Balmanoukian A, Ye X, Herman J, Laheru D, Grossman SA. The association between treatment-related lymphopenia and survival in newly diagnosed patients with resected adenocarcinoma of the pancreas. Cancer Investig. 2012;30:571–6.

    Article  Google Scholar 

  11. Lausen B, Schumacher M. Maximally selected rank statistics. Biometrics. 1992;48:73–85.

    Article  Google Scholar 

  12. Hothorn T, Lausen B. Maximally selected rank statistics in r. R News. 2002;2:3–5.

    Google Scholar 

  13. Yovino S, Grossman SA. Severity, etiology and possible consequences of treatment-related lymphopenia in patients with newly diagnosed high-grade gliomas. CNS Oncol. 2012;1:149–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zachariah B, Jacob SS, Gwede C, Cantor A, Patil J, Casey L, et al. Effect of fractionated regional external beam radiotherapy on peripheral blood cell count. Int J Radiat Oncol Biol Phys. 2001;50:465–72.

    Article  CAS  PubMed  Google Scholar 

  15. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988;319:1676–80.

    Article  CAS  PubMed  Google Scholar 

  16. Hu P, Pang Z, Shen H, Wang G, Sun H, Du J. Tumor-infiltrating neutrophils predict poor outcome in adenocarcinoma of the esophagogastric junction. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2015;36:2965–71.

    Article  CAS  Google Scholar 

  17. Kawada T. Smoking-induced leukocytosis can persist after cessation of smoking. Arch Med Res. 2004;35:246–50.

    Article  CAS  PubMed  Google Scholar 

  18. Boxer LA, Allen JM, Baehner RL. Diminished polymorphonuclear leukocyte adherence. Function dependent on release of cyclic amp by endothelial cells after stimulation of beta-receptors by epinephrine. J Clin Invest. 1980;66:268–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer. 2004;100:228–37.

    Article  PubMed  Google Scholar 

  20. Blay J, Chauvin F, Le Cesne A, Anglaret B, Bouhour D, Lasset C, et al. Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia. J Clin Oncol. 1996;14:636–43.

    Article  CAS  PubMed  Google Scholar 

  21. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther. 2013;11:55–9.

    Article  CAS  PubMed  Google Scholar 

  22. Heo J, Chun M, Noh OK, Oh YT, Suh KW, Park JE, Cho O: Sustaining blood lymphocyte count during preoperative chemoradiotherapy as a predictive marker for pathologic complete response in locally advanced rectal cancer. Cancer research and treatment : official journal of Korean Cancer Association 2015

  23. Siu LL, Shepherd FA, Murray N, Feld R, Pater J, Zee B. Influence of age on the treatment of limited-stage small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol. 1996;14:821–8.

    Article  CAS  Google Scholar 

  24. Ceze N, Thibault G, Goujon G, Viguier J, Watier H, Dorval E, et al. Pre-treatment lymphopenia as a prognostic biomarker in colorectal cancer patients receiving chemotherapy. Cancer Chemother Pharmacol. 2011;68:1305–13.

    Article  CAS  PubMed  Google Scholar 

  25. Auperin A, Arriagada R, Pignon JP, Le Pechoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341:476–84.

    Article  CAS  PubMed  Google Scholar 

  26. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357:664–72.

    Article  CAS  PubMed  Google Scholar 

  27. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992;327:1618–24.

    Article  CAS  PubMed  Google Scholar 

  28. Murray N, Coy P, Pater JL, Hodson I, Arnold A, Zee BC, et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol Off J Am Soc Clin Oncol. 1993;11:336–44.

    Article  CAS  Google Scholar 

  29. Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20:3054–60.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank all staffs related to the treatment and all the patients suffering from small cell lung cancer.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Ajou University School of Medicine, 206 World cup-ro, Yeongtong-gu, Suwon, 443-721, Republic of Korea

    Oyeon Cho, Young-Taek Oh, Mison Chun & O Kyu Noh

  2. Department of Hematology and Medical Oncology, Ajou University School of Medicine, Suwon, Republic of Korea

    Hyun-Woo Lee

Authors
  1. Oyeon Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Young-Taek Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mison Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O Kyu Noh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyun-Woo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young-Taek Oh.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

(a) The available gross tumor volumes and linear regression analysis of the 59 patients plotted against the min ALCs (b) Pearson correlation coefficients between gross tumor volume, total radiotherapy dose, and radiotherapy duration and the min ALCs or post ALCs (PDF 74 kb)

Online Resource 2

The available white blood cell count and the relative tie lines for each of the 56 patients (a) and 6 patients (b) treated with concurrent or alternate CRT and sequential CRT plotted against the radiation days. The available absolute neutrophil counts and the relative tie lines for each of the 56 patients (c) and 6 patients (d) treated with concurrent or alternate CRT and sequential CRT plotted against the radiation days (PDF 480 kb)

Online Resource 3

(DOCX 14 kb)

Online Resource 4

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cho, O., Oh, YT., Chun, M. et al. Radiation-related lymphopenia as a new prognostic factor in limited-stage small cell lung cancer. Tumor Biol. 37, 971–978 (2016). https://doi.org/10.1007/s13277-015-3888-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3888-y

Keywords

Search

Navigation