Download PDF
Thromb Haemost 2014; 111(06): 1112-1120
DOI: 10.1160/TH13-11-0956
Cellular Proteolysis and Oncology
Schattauer GmbH

Risk factors and prognostic impact of venous thromboembolism in Asian patients with non-small cell lung cancer

Yun-Gyoo Lee
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
2   Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
,
Inho Kim
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Eunyoung Lee
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Soo-Mee Bang
2   Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
,
Chang Hyun Kang
3   Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Young Tae Kim
3   Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Hak Jae Kim
4   Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Hong-Gyun Wu
4   Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Young Whan Kim
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Tae Min Kim
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Keun-Wook Lee
2   Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
,
Se-Hoon Lee
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Dong-Wan Kim
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Dae Seog Heo
1   Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
› Author Affiliations
Further Information

Publication History

Received: 19 November 2013

Accepted after major revision: 19 January 2014

Publication Date:
21 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Although the overall risk of venous thromboembolism (VTE) is high in patients with non-small cell lung cancer (NSCLC), risk identification is limited. The goal of this study was to estimate the incidence, risk factors and prognostic implications of VTE, and to evaluate a genetic link between oncogenes and the risk of VTE in Asian patients with NSCLC. A total of 1,998 consecutive patients with NSCLC were enrolled and analysed retrospectively. Since the effects of therapeutics on VTE development were modified by stage, stratified analyses were performed. When comparing overall survival in terms of VTE development, a propensity score-matching method was adopted to minimise potential confounding. The six-month and two-year cumulative incidences of VTE were 4.2% and 6.4%, respectively. The risk of VTE increased 2.45-fold with each advancing stage in NSCLC (p<0.001). The independent predictors of VTE were advanced age, pneumonectomy and palliative radiotherapy in localised NSCLC and ineligibility for surgery and palliative radiotherapy in locally advanced NSCLC. Adenocarcinoma histology (vs squamous cell) and former/current smoking status were significant predictors of VTE in metastatic NSCLC. A significant association between VTE and decreased survival was observed only among patients with localised NSCLC. EGFR mutations (p=0.170) and ALK rearrangements (p=0.159) were not associated with VTE development in lung adenocarcinoma. In conclusion, the two-year cumulative incidence of VTE is 6.4% in Asian patient with NSCLC. The significant predictors of VTE are different across stages of NSCLC. The prognostic impact of VTE on poor survival was limited to localised NSCLC.

Keywords

Venous thromboembolism - non-small cell lung carcinoma - epidermal growth factor receptor - risk factor - prognosis

 

  • References

  • 1 Rickles FR. Mechanisms of cancer-induced thrombosis in cancer. Pathophysiol Haemost Thromb 2006; 35: 103-110.
    CrossrefPubMedGoogle Scholar
  • 2 Zwicker JI, Furie BC, Furie B. Cancer-associated thrombosis. Crit Rev Oncol Hematol 2007; 62: 126-136.
    CrossrefPubMedGoogle Scholar
  • 3 Davila M, Amirkhosravi A, Coll E. et al. Tissue factor-bearing microparticles derived from tumour cells: impact on coagulation activation. J Thromb Haemost 2008; 06: 1517-1524.
    CrossrefPubMedGoogle Scholar
  • 4 Khorana AA, Francis CW, Culakova E. et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829.
    CrossrefPubMedGoogle Scholar
  • 5 Blom JW, Doggen CJ, Osanto S. et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Assoc 2005; 293: 715-722.
    CrossrefPubMedGoogle Scholar
  • 6 Heit JA, Silverstein MD, Mohr DN. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815.
    CrossrefPubMedGoogle Scholar
  • 7 Tesselaar ME, Romijn FP, Van Der Linden IK. et al. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?. J Thromb Haemost 2007; 05: 520-527.
    CrossrefPubMedGoogle Scholar
  • 8 Rak J, Milsom C, Yu J. Tissue factor in cancer. Curr Opin Hematol 2008; 15: 522-528.
    CrossrefPubMedGoogle Scholar
  • 9 Zwicker JI. Tissue factor-bearing microparticles and cancer. Semin Thromb Hemost 2008; 34: 195-198.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Boccaccio C, Comoglio PM. Genetic link between cancer and thrombosis. J Clin Oncol 2009; 27: 4827-4833.
    CrossrefPubMedGoogle Scholar
  • 11 Chew HK, Wun T, Harvey D. et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166: 458-464.
    CrossrefPubMedGoogle Scholar
  • 12 Otten HM, Mathijssen J, ten Cate H. et al. Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med 2004; 164: 190-194.
    CrossrefPubMedGoogle Scholar
  • 13 Stein PD, Beemath A, Meyers FA. et al. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 2006; 119: 60-68.
    CrossrefPubMedGoogle Scholar
  • 14 Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012; 09: e1001275.
    CrossrefPubMedGoogle Scholar
  • 15 Chew HK, Davies AM, Wun T. et al. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost 2008; 06: 601-608.
    CrossrefPubMedGoogle Scholar
  • 16 Huang H, Korn JR, Mallick R. et al. Incidence of venous thromboembolism among chemotherapy-treated patients with lung cancer and its association with mortality: a retrospective database study. J Thromb Thrombolysis 2012; 34: 446-456.
    CrossrefPubMedGoogle Scholar
  • 17 Lee KW, Bang SM, Kim S. et al. The incidence, risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer. J Thromb Haemost 2010; 08: 540-547.
    CrossrefPubMedGoogle Scholar
  • 18 Chew HK, Wun T, Harvey DJ. et al. Incidence of venous thromboembolism and the impact on survival in breast cancer patients. J Clin Oncol 2007; 25: 70-76.
    CrossrefPubMedGoogle Scholar
  • 19 Alcalay A, Wun T, Khatri V. et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 2006; 24: 1112-1118.
    CrossrefPubMedGoogle Scholar
  • 20 Greene FL. American Joint Committee on Cancer. American Cancer Society. AJCC cancer staging manual. 6th ed. New York: Springer-Verlag; 2002
    Google Scholar
  • 21 WHO. The Asia-Pacific perspective: redefining obesity and its treatment. Geneva, Switzerland: World Health Organisation; 2000
    Google Scholar
  • 22 Leuven E, Sianesi B. PSMATCH2: Stata module to perform full Mahalanobis and propensity score matching, common support graphing, and covariate imbalance testing. Statistical Software Components. 2010
    PubMedGoogle Scholar
  • 23 Ettinger DS, Akerley W, Borghaei H. et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2012; 10: 1236-1271.
    CrossrefPubMedGoogle Scholar
  • 24 Connolly GC, Menapace L, Safadjou S. et al. Prevalence and clinical significance of incidental and clinically suspected venous thromboembolism in lung cancer patients. Clin Lung Cancer 2013; 14: 713-718.
    CrossrefPubMedGoogle Scholar
  • 25 Connolly GC, Dalal M, Lin J. et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory patients with lung cancer. Lung Cancer 2012; 78: 253-258.
    CrossrefPubMedGoogle Scholar
  • 26 Ziomek S, Read RC, Tobler HG. et al. Thromboembolism in patients undergoing thoracotomy. Ann Thorac Surg 1993; 56: 223-227.
    CrossrefPubMedGoogle Scholar
  • 27 Blom JW, Osanto S, Rosendaal FR. The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost 2004; 02: 1760-1765.
    CrossrefPubMedGoogle Scholar
  • 28 Bang SM, Jang MJ, Oh D. et al. Korean guidelines for the prevention of venous thromboembolism. J Korean Med Sci 2010; 25: 1553-1559.
    CrossrefPubMedGoogle Scholar
  • 29 Rodriguez AO, Wun T, Chew H. et al. Venous thromboembolism in ovarian cancer. Gynecol Oncol 2007; 105: 784-790.
    CrossrefPubMedGoogle Scholar
  • 30 Yang Y, Zhou Z, Niu XM. et al. Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients. J Surg Oncol 2012; 106: 736-741.
    CrossrefPubMedGoogle Scholar
  • 31 Yu JL, May L, Lhotak V. et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumour progression and angiogenesis. Blood 2005; 105: 1734-1741.
    CrossrefPubMedGoogle Scholar