Thromboembolism in lung cancer – An area of urgent unmet need
Introduction
Lung cancer (LC) is the most common cause of cancer mortality in many countries, including Australia. Thromboembolism (TE) is reported in up to 14% of LC patients, a 20-fold increased risk in comparison to the general population and among the highest incidences of all cancer populations [1], [2], [3].
Cancer-associated thrombosis has substantial adverse health and economic consequences [4], [5]. It is a potent negative predictor of survival and a leading cause of death [1], [6]. Appropriate pharmacological thromboprophylaxis (P-TP) can be a highly cost-effective preventative strategy with the potential to reduce the incidence of TE in high-risk patients by up to 80% [7], [8], [9]. While all patients with cancer should be considered at risk of TE, the risk is dynamic, and the absolute magnitude and duration of TE risk is not equal for all patients or for a given individual over time. This heterogeneity in both TE and bleeding risk is further exaggerated during the cancer disease course and different intervention phases – emphasising the importance of a personalised risk-stratified approach rather than a broad application of P-TP in patients with cancer.
There is substantial variation in the TE incidence reported among LC patients (2–14%), which likely reflects this dynamic risk profile [1], [2], [3], [5], [10], [11], [12], [13], [14], [15], [16]. Reported rates likely underestimate the true incidence as registry data cannot adequately capture outpatient management, the arena in which the majority of LC patients are treated. Chemotherapy is one of the most important treatment-related factors in the aetiology of cancer associated TE, with most events occurring in the ambulatory care setting [16], [17], [18], [19], [20]. Subgroup analysis of LC patients within several large scale randomised studies of cancer patients undergoing chemotherapy demonstrated both safety and efficacy of P-TP in this setting [21], [22], [23]. The overall post-surgical TE incidence in LC (10.1%) is higher than the overall incidence rate among all cancers, and second only to gastrointestinal cancers [24]. All major international guidelines recommend P-TP in this setting; however the duration of therapy remains contentious [25], [26], [27], [28], [29], [30]. Recent studies have demonstrated an extended period of TE risk for cancer patients, particularly following major surgery, beyond the standard 7–10 days of recommended P-TP [31]. Despite LC being the second most common cause of cancer associated TE in the post-surgical setting there is a lack of data defining the optimal duration of P-TP [25], [26], [27], [28], [29], [30].
This retrospective cohort study reports the incidence and timing of TE across different stages of treatment (surgery, radiotherapy, chemotherapy and biologic agents) for a subset of LC patients treated at a dedicated cancer centre over a 12 month period.
Section snippets
Patient population
All LC patents referred to the Peter MacCallum Cancer Centre (Peter Mac) lung unit during the period 01/07/12–30/06/13 were screened for inclusion. Eligible patients had a diagnosis of small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), any disease stage (stage I–IV), and any disease status (newly diagnosed or pre-treated). Patients with a non-LC diagnosis and patients not receiving treatment primarily at Peter Mac (i.e. referred for opinion or staging only) were excluded.
Study design
A
Patients and treatment
804 patients were referred to the Peter Mac lung unit during the study period; 222 were eligible for inclusion (Fig. 1). The median period of follow-up from first hospital registration was 10.0 months (range: 0.03–32 months). Patients were followed for a total of 183.4 person-years. Patient characteristics are summarised in Table 1 with the majority being newly diagnosed disease (>75%), and with advanced disease (stage III–IV NSCLC, extensive disease SCLC) (>70%), NSCLC (>90%) and
Discussion
The reported TE rate in this single institution study (10.8%) exceeds that reported in a US study of more than 90,000 LC patients, which reported a 2-year cumulative TE incidence of just 3% [10]. Although published in 2008, this population-based study reports on patients diagnosed with LC more than a decade ago (1993–1999). TE rates reported in smaller but more recent studies (8–14%) [13], [14], [15], [16] align with reported figures in this study and may provide better representation of
Conclusion
Efforts to reduce the burden of cancer associated TE may have significant impact on reducing morbidity, mortality and health care resource utilisation, as well as optimising delivery of cancer therapy – but there is a need for appropriate risk-stratification and directed preventative strategies. LC patients are at high risk of preventable and life-threatening thrombotic events. The majority of TE events occur in the ambulatory care setting and consideration for P-TP is warranted, but is not
Funding
None declared.
Conflict of interest statement
None declared.
References (46)
- et al.
The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma
J Thromb Haemost
(2004) - et al.
The MASTER registry on venous thromboembolism: description of the study cohort
Thromb Res
(2008) - et al.
Benefits of deep-vein thrombosis prophylaxis in the nonsurgical patient: The MEDENOX trial
Semin Hematol
(2001) - et al.
The incidence of venous thromboembolism among patients with primary lung cancer
J Thromb Haemost
(2008) - et al.
Incidence of venous thromboembolism in patients hospitalized with cancer
Am J Med
(2006) - et al.
High risk of deep vein thrombosis in patients with non-small cell lung cancer: a cohort study of 493 patients
J Thorac Oncol
(2007) - et al.
Incidence and predictors of venous thromboembolism (VTE) among ambulatory patients with lung cancer
Lung Cancer
(2012) - et al.
Incidence of venous thromboembolism in hospitalized patients vs community residents
Mayo Clin Proc
(2001) - et al.
Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy
J Thromb Haemost
(2007) - et al.
Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study
Lancet Oncol
(2009)