Elsevier

Lung Cancer

Volume 84, Issue 3, June 2014, Pages 275-280
Lung Cancer

Thromboembolism in lung cancer – An area of urgent unmet need

https://doi.org/10.1016/j.lungcan.2014.02.009Get rights and content

Abstract

Introduction

Thromboembolism is common in lung cancer. Current thromboprophylaxis guidelines lack specific recommendations for appropriate strategies in this high thrombotic risk patient cohort. We profiled lung cancer patients receiving anti-cancer therapy. Thromboembolism incidence and thromboembolism-related mortality rates are reported and we explored patient, disease, and treatment-related risk factors associated with higher thrombotic rates.

Methods

Retrospective review of lung cancer patients referred to a Comprehensive Cancer Centre between 01/07/2011 and 30/06/2012 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records.

Results

After a median follow up of 10 months (range: 0.03–32 months), 24/222 patients (10.8%) had developed radiologically confirmed thromboembolism; 131 events per 1000 person-years (95%CI 87–195). Thromboembolism occurred equally in patients with non-small cell and small cell lung cancer (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell carcinoma (14.7% and 5.3% respectively). Chemotherapy-treated patients experienced thromboembolism more often than patients who did not receive chemotherapy (HR 5.7 95%CI 2.2–14.8). Radiotherapy was also associated with more frequent thromboembolism (HR 5.2 95%CI 2.0–13.2). New lung cancer diagnosis, presence of metastatic disease, second primary malignancy and Charlson Index ≥5 were also associated with higher rates of thromboembolism. Importantly, pharmacological thromboprophylaxis (P-TP) was not routinely or systematically prescribed for ambulant lung cancer patients during any treatment phase, at this institution. The majority (83%) of thromboembolic events occurred in the ambulatory care setting.

Conclusion

Morbidity and mortality from thromboembolism occurs frequently in lung cancer. Thromboprophylaxis guidelines should be developed for the ambulatory care setting.

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)

  • M. Mandalà et al.

    Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines

    Ann Oncol

    (2011)
  • W.H. Geerts et al.

    Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition)

    Chest

    (2008)
  • M.E. Charlson et al.

    A new method of classifying prognostic comorbidity in longitudinal studies: development and validation

    J Chronic Dis

    (1987)
  • M. Carrier et al.

    Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies

    J Thromb Haemost

    (2010)
  • R.D. Malgor et al.

    A systematic review of pulmonary embolism in patients with lung cancer

    Ann Thorac Surg

    (2012)
  • F. Dentali et al.

    Prevalence and clinical history of incidental, asymptomatic pulmonary embolism: a meta-analysis

    Thromb Res

    (2010)
  • F.W. Dekker et al.

    Survival analysis: time-dependent effects and time-varying risk factors

    Kidney Int

    (2008)
  • H.K. Chew et al.

    Incidence of venous thromboembolism and its effect on survival among patients with common cancers

    Arch Intern Med

    (2006)
  • J.W. Blom et al.

    Malignancies, prothrombotic mutations, and the risk of venous thrombosis

    JAMA

    (2005)
  • A.A. Khorana et al.

    Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients

    Cancer

    (2007)
  • N.M. Kuderer et al.

    Impact of venous thromboembolism and anticoagulation on cancer and cancer survival

    J Clin Oncol

    (2009)
  • E.A. Akl et al.

    Low-molecular-weight heparin vs unfractionated heparin for perioperative thromboprophylaxis in patients with cancer: a systematic review and meta-analysis

    Arch Intern Med

    (2008)
  • P. Mismetti et al.

    Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery

    Br J Surg

    (2001)
  • Cited by (0)

    View full text