Lung cancer is associated with a very high risk of developing venous thromboembolism (VTE).
In a large population-based, case–control study, lung cancer was associated with a very high relative risk of VTE, with the highest adjusted odds ratio (OR; 22.2; 95% CI: 3.6–136.1) of all malignancies after hematological malignancy (adjusted OR, 28.0; 95% CI: 4.0–199.7) and before gastrointestinal cancer (adjusted OR, 20.3; 95% C: 4.9–83.0) .
In a prospective observational study on patients with lung cancer, the incidence of VTE was 11.3% (95% CI: 9.2–13.7%) before chemotherapy treatment and 16.8% (95% CI: 14.2–19.6%) and 14.1% (95% CI: 11.6–16.9%) at 12 and 24 weeks after the start of chemotherapy, respectively .
In a retrospective cohort analysis in patients with lung cancer who underwent chemotherapy, VTE occurred in 13.9% of the lung cancer cohort compared to 1.4% of the control cohort at 12 months of follow-up .
VTE can anticipate a cancer diagnosis, and patients may be in a hypercoagulable state before the start of lung cancer treatment .
Moreover, the occurrence of VTE may increase the severity of patients’ conditions, and it is associated with a higher probability of death in patients with primary lung cancer. A large population-based study showed that 3% of patients with non-small-cell and small-cell lung cancer developed VTE within 2 years, and VTE was associated with a higher risk of death .
VTE risk factors in patients with lung cancer
Several risk factors are associated with high-risk VTE in patients with lung cancer.
Advanced tumor stage, metastatic disease, and a history of or current adenocarcinoma subtype are independent risk factors for VTE [6, 7]. Patients with adenocarcinoma, especially if metastatic, have a higher risk compared to those with squamous cell carcinoma .
In addition, gene mutations can play a role. Patients with mutations in ROS1, ALK and KRAS, and NSCLC have an increased risk of VTE.
A study comparing patients with KRAS, ROS, and EGFR-positive lung cancers found that those with ROS-mutated cancer had a significantly higher risk of VTE . A phase II, prospective, multicenter, two-arm trial confirmed a 3–5-times higher risk of VTE in patients with ROS1-rearranged NSCLC than the general population .
Another study found the same increase in VTE risk (3–5-times) in patients with ALK-mutated NSCLC compared to the general population .
As for other cancer types, chemotherapy treatment influences the risk of VTE in patients with lung cancer. VTE occurs more often within 6 months after the initiation of the chemotherapy regimen, and it carries an increased risk of mortality .
Cisplatin-based regimens are associated with a higher risk of VTE compared to other types. In addition, the use of anti-VEGF drugs increases the risk of arterial thromboembolic events but not VTE .
Other risk factors are patient-related. It has been shown that people with lung cancer and those aged below 45 years have about three-times higher risk of VTE if compared with people in the same conditions but older than 75 years .
Ethnicity is another risk factor, with African–Americans carrying the higher risk and Asians having the lowest incidence .
Finally, patients with atrial fibrillation and chronic kidney disease are more likely to develop VTE .
Risk assessment tools
A few risk assessment methods have been validated for lung cancer. Risk assessment tools allow predicting the risk of VTE in a particular subset of patients.
Finally, the COMPASS-CAT score is the most complicated model, considering both cancer-related and patient-related factors. It has been validated in patients with lung cancer, but two different cut-offs have been used in different studies .
Compared to Khorana, the COMPASS-CAT score has higher sensitivity (86% with a cut-off value of 7 and 100% with a cut-off value of 11), but it has a lower specificity (35–51%). This means that about half or two-thirds of patients who did not develop VTE have been classified as high risk. The cut-off value of 11 showed a C-index of 0.89, but it needs further validation .
A study compared the PROTECHT score, the COMPASS-CAT, the CONKO score, and the Khorana risk score. The COMPASS-CAT score was able to efficiently differentiate among high- and low-risk patients with VTE and, compared to the other risk models, had the best performance for VTE prediction in patients with lung cancer .
If you want to read more about VTE risk scores, check out “Risk assessment models for venous thromboembolism in ambulatory patients with cancer: A talk with Prof. Gerotziafas.”
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