Medical Oncology

, Volume 29, Issue 5, pp 3176–3182 | Cite as

Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer

  • Georg Holgersson
  • Martin Sandelin
  • Even Hoye
  • Stefan Bergström
  • Roger Henriksson
  • Simon Ekman
  • Jan Nyman
  • Martin Helsing
  • Signe Friesland
  • Margareta Holgersson
  • Kristina Lamberg Lundström
  • Christer Janson
  • Elisabet Birath
  • Charlotte Mörth
  • Thomas Blystad
  • Sven-Börje Ewers
  • Britta Löden
  • Michael Bergqvist
Original Paper

Abstract

There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (>50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb < 110 g/L and Hgb ≥ 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC > 9.0 × 109/L and < 9.0 × 109/L, the median survival was 11.6 and 15.4 months, respectively (p < 0.0001). For Plt > 350 × 109/L and <350 × 109/L, the median survival was 11.2 and 14.9 months, respectively (p < 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p < 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.

Keywords

Non-small cell lung cancer Prognosis Biomarker Anaemia Thrombocytosis Leukocytosis 

Notes

Acknowledgments

The authors would like to thank Stiftelsen Gävle Cancerfond and Professor John Naeslunds stipendiefond for generously providing funds for this project. Also, the authors would like to thank Ola Brodin, Peter Ericsson, Claes Mercke, Enyat Mavadati, Andrzej Piwowar, Ingemar Sandin, Daniel Brattström, Shirin Mavadati and Mats Fagerlind who have helped with the gathering of patients and their medical charts as well as with the building of databases and the input of data into it.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

12032_2012_247_MOESM1_ESM.pdf (83 kb)
Online resource 1: Patient characteristics, treatment, relapse and cause of death (PDF 83 kb)
12032_2012_247_MOESM2_ESM.pdf (56 kb)
Online Resource 2: Estimated median survival and 5-year survival rate for patients with different lab risk factors (PDF 55 kb)

References

  1. 1.
    Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001;37(Suppl 8):S4–66.PubMedCrossRefGoogle Scholar
  2. 2.
    Bolton WD, Rice DC, Correa AM, Hofstetter W, Komaki R, Mehran R et al. Influence of age on choice of therapy and surgical outcomes in patients with nonsmall cell lung cancer. Am Surg. 2009;75(7):598–603; discussion 4.Google Scholar
  3. 3.
    Spiro SG, Porter JC. Lung cancer–where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med. 2002;166(9):1166–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Spiro SG, Silvestri GA. The treatment of advanced non-small cell lung cancer. Curr Opin Pulm Med. 2005;11(4):287–91.PubMedCrossRefGoogle Scholar
  5. 5.
    Sato M, Shames DS, Gazdar AF, Minna JD. A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol. 2007;2(4):327–43. doi: 10.1097/01.JTO.0000263718.69320.4c.PubMedCrossRefGoogle Scholar
  6. 6.
    Clark GM. Prognostic factors versus predictive factors: examples from a clinical trial of erlotinib. Mol Oncol. 2008;1(4):406–12. doi: 10.1016/j.molonc.2007.12.001.PubMedCrossRefGoogle Scholar
  7. 7.
    Chamogeorgakis T, Anagnostopoulos C, Kostopanagiotou G, Bhora F, Toumpoulis I, Georgiannakis E, et al. Does anemia affect outcome after lobectomy or pneumonectomy in early stage lung cancer patients who have not received neo-adjuvant treatment? Thorac Cardiovasc Surg. 2008;56(3):148–53. doi: 10.1055/s-2007-989455.PubMedCrossRefGoogle Scholar
  8. 8.
    Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T. Impact of preoperative hemoglobin level on survival of non-small cell lung cancer patients. Anticancer Res. 2008;28(3):1947–50.PubMedGoogle Scholar
  9. 9.
    MacRae R, Shyr Y, Johnson D, Choy H. Declining hemoglobin during chemoradiotherapy for locally advanced non-small cell lung cancer is significant. Radiother Oncol. 2002;64(1):37–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Kasuga I, Makino S, Kiyokawa H, Katoh H, Ebihara Y, Ohyashiki K. Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma. Cancer. 2001;92(9):2399–405. doi: 10.1002/1097-0142(20011101)92:9<2399:AID-CNCR1588>3.0.CO;2-W.PubMedCrossRefGoogle Scholar
  11. 11.
    Ferrigno D, Buccheri G. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients. Monaldi Arch Chest Dis. 2003;59(3):193–8.PubMedGoogle Scholar
  12. 12.
    Thomson SP, Kessler JF, Miller TP. Leukocyte concentrations in discrimination of benign from malignant lung lesions. Am J Med. 1986;80(6):1035–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T. Prognostic impact of thrombocytosis in resectable non-small cell lung cancer. Interact Cardiovasc Thorac Surg. 2008;7(4):613–5. doi: 10.1510/icvts.2007.174391.PubMedCrossRefGoogle Scholar
  14. 14.
    Gislason T, Nou E. Sedimentation rate, leucocytes, platelet count and haemoglobin in bronchial carcinoma: an epidemiological study. Eur J Respir Dis. 1985;66(2):141–6.PubMedGoogle Scholar
  15. 15.
    Engan T, Hannisdal E. Blood analyses as prognostic factors in primary lung cancer. Acta Oncol. 1990;29(2):151–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Pedersen LM, Milman N. Prognostic significance of thrombocytosis in patients with primary lung cancer. Eur Respir J. 1996;9(9):1826–30.PubMedCrossRefGoogle Scholar
  17. 17.
    Aoe K, Hiraki A, Ueoka H, Kiura K, Tabata M, Tanaka M, et al. Thrombocytosis as a useful prognostic indicator in patients with lung cancer. Respiration. 2004;71(2):170–3. doi: 10.1159/000076679.PubMedCrossRefGoogle Scholar
  18. 18.
    Costantini V, Zacharski LR, Moritz TE, Edwards RL. The platelet count in carcinoma of the lung and colon. Thromb Haemost. 1990;64(4):501–5.PubMedGoogle Scholar
  19. 19.
    Mandrekar SJ, Schild SE, Hillman SL, Allen KL, Marks RS, Mailliard JA, et al. A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials. Cancer. 2006;107(4):781–92. doi: 10.1002/cncr.22049.PubMedCrossRefGoogle Scholar
  20. 20.
    Maione P, Rossi A, Di Maio M, Gridelli C. Tumor-related leucocytosis and chemotherapy-induced neutropenia: linked or independent prognostic factors for advanced non-small cell lung cancer? Lung Cancer. 2009;66(1):8–14. doi: 10.1016/j.lungcan.2009.02.022.PubMedCrossRefGoogle Scholar
  21. 21.
    Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol. 1991;9(9):1618–26.PubMedGoogle Scholar
  22. 22.
    Stinchcombe TE, Hodgson L, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, et al. Treatment outcomes of different prognostic groups of patients on cancer and leukemia group B trial 39801: induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for unresectable stage III non-small cell lung cancer. J Thorac Oncol. 2009;4(9):1117–25. doi: 10.1097/JTO.0b013e3181b27b33.PubMedCrossRefGoogle Scholar
  23. 23.
    Mandrekar SJ, Northfelt DW, Schild SE, Foster NR, Bot B, Marks RS, et al. Impact of pretreatment factors on adverse events: a pooled analysis of North Central Cancer Treatment Group advanced stage non-small cell lung cancer trials. J Thorac Oncol. 2006;1(6):556–63.PubMedCrossRefGoogle Scholar
  24. 24.
    Suda T, Miura Y, Mizoguchi H, Kubota K, Takaku F. A case of lung cancer associated with granulocytosis and production of colony-stimulating activity by the tumour. Br J Cancer. 1980;41(6):980–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Shijubo N, Inoue Y, Hirasawa M, Igarashi T, Mori M, Matsuura A, et al. Granulocyte colony-stimulating factor-producing large cell undifferentiated carcinoma of the lung. Intern Med. 1992;31(2):277–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Harrison L, Blackwell K. Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy? Oncologist. 2004;9(Suppl 5):31–40. doi: 10.1634/theoncologist.9-90005-31.PubMedCrossRefGoogle Scholar
  27. 27.
    Vaupel P, Briest S, Hockel M. Hypoxia in breast cancer: pathogenesis, characterization and biological/therapeutic implications. Wien Med Wochenschr. 2002;152(13–14):334–42.PubMedCrossRefGoogle Scholar
  28. 28.
    Vaupel P, Thews O, Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol. 2001;18(4):243–59. doi: 10.1385/MO:18:4:243.PubMedCrossRefGoogle Scholar
  29. 29.
    Teicher BA. Physiologic mechanisms of therapeutic resistance. Blood flow and hypoxia. Hematol Oncol Clin North Am. 1995;9(2):475–506.PubMedGoogle Scholar
  30. 30.
    Mehta P. Potential role of platelets in the pathogenesis of tumor metastasis. Blood. 1984;63(1):55–63.PubMedGoogle Scholar
  31. 31.
    Karpatkin S, Pearlstein E. Role of platelets in tumor cell metastases. Ann Intern Med. 1981;95(5):636–41.PubMedGoogle Scholar
  32. 32.
    Gastpar H, Ambrus JL, Ambrus CM. Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors: a possible approach to metastasis prevention. Prog Clin Biol Res. 1982;89:63–82.PubMedGoogle Scholar
  33. 33.
    Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T. Preoperative leukocytosis, anemia and thrombocytosis are associated with poor survival in non-small cell lung cancer. Anticancer Res. 2009;29(7):2687–90.PubMedGoogle Scholar
  34. 34.
    Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733–42. doi: 10.1056/NEJMoa1000678.PubMedCrossRefGoogle Scholar
  35. 35.
    Shopland DR. Tobacco use and its contribution to early cancer mortality with a special emphasis on cigarette smoking. Environ Health Perspect. 1995;103(Suppl 8):131–42.PubMedCrossRefGoogle Scholar
  36. 36.
    Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429–35. doi: 10.1002/cncr.22963.PubMedCrossRefGoogle Scholar
  37. 37.
    Liu BQ, Peto R, Chen ZM, Boreham J, Wu YP, Li JY, et al. Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths. BMJ. 1998;317(7170):1411–22.PubMedCrossRefGoogle Scholar
  38. 38.
    Soo RA, Anderson BO, Cho BC, Yang CH, Liao M, Lim WT, et al. First-line systemic treatment of advanced stage non-small-cell lung cancer in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009;10(11):1102–10. doi: 10.1016/S1470-2045(09)70238-4.PubMedCrossRefGoogle Scholar
  39. 39.
    Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001;2(9):533–43. doi: 10.1016/S1470-2045(01)00486-7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Georg Holgersson
    • 1
  • Martin Sandelin
    • 2
  • Even Hoye
    • 3
  • Stefan Bergström
    • 3
  • Roger Henriksson
    • 4
  • Simon Ekman
    • 1
  • Jan Nyman
    • 5
  • Martin Helsing
    • 7
  • Signe Friesland
    • 6
  • Margareta Holgersson
    • 1
  • Kristina Lamberg Lundström
    • 2
  • Christer Janson
    • 2
  • Elisabet Birath
    • 7
  • Charlotte Mörth
    • 1
  • Thomas Blystad
    • 8
  • Sven-Börje Ewers
    • 9
  • Britta Löden
    • 10
  • Michael Bergqvist
    • 1
  1. 1.Section of Oncology, Department of Radiology, Oncology and Radiation SciencesUppsala UniversityUppsalaSweden
  2. 2.Department of Medical Sciences, Respiratory MedicineUppsala UniversityUppsalaSweden
  3. 3.Department of OncologyGävle HospitalGävleSweden
  4. 4.Department of OncologyUmeå University HospitalUmeåSweden
  5. 5.Department of OncologySahlgrenska University HospitalGöteborgSweden
  6. 6.Karolinska University HospitalStockholmSweden
  7. 7.Department of OncologySkåne University HospitalMalmöSweden
  8. 8.Department of General OncologyLinköping University HospitalLinköpingSweden
  9. 9.Department of OncologyLund University HospitalLundSweden
  10. 10.Department of OncologyCentral HospitalKarlstadSweden

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