Skip to main content

Advertisement

Log in

Difference in survival and prognostic factors between smokers and never-smokers with advanced non-small-cell lung cancer

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Our aims were to investigate whether the association between smoking and survival is significant when adjusted for prognostic factors including use of epidermal growth factor tyrosine kinase inhibitors and the Glasgow Prognostic Score, an established score for inflammation, and to explore prognostic factors.

Methods

We analyzed 244 patients with stage IIIB or IV non-small-cell lung cancer in a registry, including only chemotherapy-receiving outpatients with performance status zero.

Results

Of 244 patients, 170 had died and the median follow-up time for the 74 surviving patients was 12.0 months. In multivariate Cox regression, smoker (hazard ratio compared to never-smoker: 1.67, P < 0.01), stage IV (hazard ratio compared to IIIB: 1.72, P < 0.01), and elevated C-reactive protein level (hazard ratio per 1 mg/dL increase: 1.08, P < 0.01) were significantly associated with shorter survival. The association between survival and smoking was significant, even after adjustment for the Glasgow Prognostic Score and regimens of chemotherapy (hazard ratio: 1.72, P = 0.02). In never-smokers, increased neutrophils were a major determinant of shorter survival and the interaction test between smoking and neutrophils was significant (hazard ratio per 1,000/mm3 increase for smokers: 1.01; hazard ratio per 1,000/mm3 increase for never-smokers: 1.44, P for interaction <0.01).

Conclusions

Known factors including treatment response or inflammatory process are not responsible for the fact that advanced non-small-cell lung cancer patients without any history of smoking have better survival than those who have smoked.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chen CJ, Wu HY, Chuang YC et al (1990) Epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan. Anticancer Res 10:971–976

    PubMed  CAS  Google Scholar 

  2. Toh CK, Gao F, Lim WT et al (2006) Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol 20:2245–2251

    Article  Google Scholar 

  3. Wakelee HA, Chang ET, Gomez SL et al (2007) Lung cancer incidence in never smokers. J Clin Oncol 25:472–478

    Article  PubMed  Google Scholar 

  4. Sun S, Schiller JH, Gazdar AF (2007) Lung cancer in never smokers—a different disease. Nat Rev Cancer 7:778–7790

    Article  PubMed  CAS  Google Scholar 

  5. Subramanian J, Govindan R (2007) Lung cancer in never smokers: a review. J Clin Oncol 10:561–570

    Article  Google Scholar 

  6. Fujisawa T, Iizasa T, Saitoh Y et al (1999) Smoking before surgery predicts poor long-term survival in patients with stage I non-small-cell lung carcinomas. J Clin Oncol 17:2086–2091

    PubMed  CAS  Google Scholar 

  7. Tammemagi CM, Neslund-Dudas C, Simoff M et al (2004) Smoking and lung cancer survival: the role of comorbidity and treatment. Chest 125:27–37

    Article  PubMed  Google Scholar 

  8. Nordquist LT, Simon GR, Cantor A et al (2004) Improved survival in never-smokers versus current smokers with primary adenocarcinoma of the lung. Chest 126:347–351

    Article  PubMed  Google Scholar 

  9. Toh CK, Wong EH, Lim WT et al (2004) The impact of smoking status on the behavior and survival outcome of patients with advanced non-small cell lung cancer: a retrospective analysis. Chest 126:1750–1756

    Article  PubMed  Google Scholar 

  10. Kawai H, Tada A, Kawahara M et al (2005) Smoking history before surgery and prognosis in patients with stage IA non-small-cell lung cancer-a multicenter study. Lung Cancer 49:63–70

    Article  PubMed  Google Scholar 

  11. Tsao AS, Liu D, Lee JJ et al (2006) Smoking affects treatment outcome in patients with advanced nonsmall cell lung cancer. Cancer 106:2428–2436

    Article  PubMed  Google Scholar 

  12. Zhou W, Heist RS, Liu G et al (2006) Smoking cessation before diagnosis and survival in early stage non-small cell lung cancer patients. Lung Cancer 53:375–380

    Article  PubMed  Google Scholar 

  13. Bryant A, Cerfolio RJ (2007) Differences in epidemiology, histology, and survival between cigarette smokers and never-smokers who develop non-small cell lung cancer. Chest 132:185–192

    Article  PubMed  Google Scholar 

  14. Subramanian J, Velcheti V, Gao F et al (2007) Presentation and stage-specific outcomes of lifelong never-smokers with non-small cell lung cancer (NSCLC). J Thorac Oncol 2:827–830

    Article  PubMed  Google Scholar 

  15. Itaya T, Yamaoto N, Ando M et al (2007) Influence of histological type, smoking history and chemotherapy on survival after first-line therapy in patients with advanced non-small cell lung cancer. Cancer Sci 98:226–230

    Article  PubMed  CAS  Google Scholar 

  16. Hanagiri T, Sugio K, Mizukami M et al (2008) Significance of smoking as a postoperative prognostic factor in patients with non-small cell lung cancer. J Thorac Oncol 3:1127–1132

    Article  PubMed  Google Scholar 

  17. Guo NL, Tosun K, Horn K (2009) Impact and interactions between smoking and traditional prognostic factors in lung cancer progression. Lung Cancer 66:386–392

    Article  PubMed  Google Scholar 

  18. Teramukai S, Kitano T, Kishida Y et al (2009) 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 45:1950–1958

    Article  PubMed  Google Scholar 

  19. Shepherd FA, Dancey J, Ramlau R et al (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132

    Article  PubMed  CAS  Google Scholar 

  20. Thatcher N, Chang A, Parikh P et al (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366:1527–1537

    Article  PubMed  CAS  Google Scholar 

  21. Zhang Z, Xu F, Wang S et al (2008) Influence of smoking on histologic type and the efficacy of adjuvant chemotherapy in resected non-small cell lung cancer. Lung Cancer 60:434–440

    Article  PubMed  Google Scholar 

  22. Yanbaeva DG, Dentener MA, Creutzberg EC et al (2007) Systemic effects of smoking. Chest 131:1557–1566

    Article  PubMed  CAS  Google Scholar 

  23. Scott HR, McMillan DC, Forrest LM et al (2002) The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 87:264–267

    Article  PubMed  CAS  Google Scholar 

  24. Forrest McMillan DC, McArdle CS et al (2005) A prospective longitudinal study of performance status, an inflammation-based score (GPS) and survival in patients with inoperable non-small-cell lung cancer. Br J Cancer 23:1834–1836

    Article  Google Scholar 

  25. Wilop S, Crysandt M, Bendel M et al (2008) Correlation of C-reactive protein with survival and radiographic response to first-line platinum-based chemotherapy in advanced non-small cell lung cancer. Onkologie 31:665–670

    Article  PubMed  CAS  Google Scholar 

  26. Koch A, Fohlin H, Sörenson S (2009) Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy. J Thorac Oncol 4:326–332

    Article  PubMed  Google Scholar 

  27. Paesmans M, Sculier JP, Libert P et al (1995) Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party. J Clin Oncol 13:1221–1230

    PubMed  CAS  Google Scholar 

  28. Watine J (2000) Prognostic evaluation of primary non-small cell lung carcinoma patients using biological fluid variables. A systematic review. Scand J Clin Lab Invest 60:259–274

    Article  PubMed  CAS  Google Scholar 

  29. Nakahara Y, Mochiduki Y, Miyamoto Y et al (2005) Prognostic significance of the lymphocyte-to-neutrophil ratio in percutaneous fine-needle aspiration biopsy specimens of advanced nonsmall cell lung carcinoma. Cancer 104:1271–1280

    Article  PubMed  Google Scholar 

  30. Mandrekar SJ, Schild SE, Hillman SL et al (2006) A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials. Cancer 15:781–792

    Article  Google Scholar 

  31. Sarraf KM, Belcher E, Raevsky E et al (2009) Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. Thorac Cardiovasc Surg 137:425–428

    Article  Google Scholar 

  32. Yamamoto K, Matsumoto S, Tada H et al (2008) A data capture system for outcomes studies that integrates with electronic health records: development and potential uses. J Med Syst 32:423–427

    Article  PubMed  Google Scholar 

  33. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  34. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  35. Mantovani A, Allavena P, Sica A et al (2008) Cancer-related inflammation. Nature 454:436–444

    Article  PubMed  CAS  Google Scholar 

  36. Lewkowicz P, Lewkowicz N, Sasiak A, Tchorzewski H (2006) Lipopolysaccharide-activated CD4+ CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death. J Immunol 15:7155–7163

    Google Scholar 

Download references

Conflict of interest

K. Yanagihara received research funding from Taiho Pharmaceutical and Chugai Pharmaceutical. The other authors declare no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shiro Tanaka.

Additional information

S. Tanaka, K. Yanagihara and S. Tamaru contributed equally to this work.

About this article

Cite this article

Tanaka, S., Yanagihara, K., Tamaru, S. et al. Difference in survival and prognostic factors between smokers and never-smokers with advanced non-small-cell lung cancer. Int J Clin Oncol 18, 17–25 (2013). https://doi.org/10.1007/s10147-011-0334-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-011-0334-z

Keywords

Navigation