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

Yun-Gyoo Lee; Inho Kim; Eunyoung Lee; Soo-Mee Bang; Chang Hyun Kang; Young Tae Kim; Hak Jae Kim; Hong-Gyun Wu; Young Whan Kim; Tae Min Kim; Keun-Wook Lee; Se-Hoon Lee; Dong-Wan Kim; Dae Seog Heo

doi:10.1160/TH13-11-0956

Thrombosis and Haemostasis, Table of Contents

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

Authors

Yun-Gyoo Lee

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

²Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
Inho Kim

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Eunyoung Lee

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Soo-Mee Bang

²Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
Chang Hyun Kang

³Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Young Tae Kim

³Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Hak Jae Kim

⁴Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Hong-Gyun Wu

⁴Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Young Whan Kim

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Tae Min Kim

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Keun-Wook Lee

²Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
Se-Hoon Lee

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Dong-Wan Kim

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Dae Seog Heo

¹Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

Abstract

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

Full Text

References

References
1 Rickles FR. Mechanisms of cancer-induced thrombosis in cancer. Pathophysiol Haemost Thromb 2006; 35: 103-110.
2 Zwicker JI, Furie BC, Furie B. Cancer-associated thrombosis. Crit Rev Oncol Hematol 2007; 62: 126-136.
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.
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.
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.
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.
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.
8 Rak J, Milsom C, Yu J. Tissue factor in cancer. Curr Opin Hematol 2008; 15: 522-528.
9 Zwicker JI. Tissue factor-bearing microparticles and cancer. Semin Thromb Hemost 2008; 34: 195-198.
10 Boccaccio C, Comoglio PM. Genetic link between cancer and thrombosis. J Clin Oncol 2009; 27: 4827-4833.
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.
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.
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.
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.
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.
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.
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.
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.
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.
20 Greene FL. American Joint Committee on Cancer. American Cancer Society. AJCC cancer staging manual. 6th ed. New York: Springer-Verlag; 2002
21 WHO. The Asia-Pacific perspective: redefining obesity and its treatment. Geneva, Switzerland: World Health Organisation; 2000
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
23 Ettinger DS, Akerley W, Borghaei H. et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2012; 10: 1236-1271.
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.
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.
26 Ziomek S, Read RC, Tobler HG. et al. Thromboembolism in patients undergoing thoracotomy. Ann Thorac Surg 1993; 56: 223-227.
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.
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.
29 Rodriguez AO, Wun T, Chew H. et al. Venous thromboembolism in ovarian cancer. Gynecol Oncol 2007; 105: 784-790.
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.
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.

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