Driver Genes Associated With the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Xiaohan Qian, Mengjiao Fu, Jing Zheng, Jianya Zhou, Jianying Zhou, Xiaohan Qian, Mengjiao Fu, Jing Zheng, Jianya Zhou, Jianying Zhou

Abstract

Background: The association between driver genes and the incidence of thromboembolic events (TEs) in patients diagnosed with non-small-cell lung cancer (NSCLC) needs to be quantified to guide clinical management.

Methods: We interrogated PubMed, Embase, Web of Science and Cochrane library databases for terms related to venous thromboembolism (VTE) and arterial thromboembolism (ATE) in patients diagnosed with non-small-cell lung cancer harboring driver genes. This search was conducted for studies published between 1 January, 2000 and 31 December, 2020. A random-effects meta-analysis was performed to analyze the pooled incidence and odds ratios of VTE in patients with different driver genes.

Results: Of the 2,742 citations identified, a total of 25 studies that included 21,156 patients met eligibility criteria. The overall pooled incidence of VTE in patients with driver genes was 23% (95% CI 18-29). Patients with ROS1 rearrangements had the highest incidence of VTE (37%, 95%CI 23-52). ALK rearrangements were associated with increased VTE risks (OR=2.08,95% CI 1.69-2.55), with the second highest incidence of VTE (27%, 95%CI 20-35). Both groups of patients with EGFR and KRAS mutations did not show a significantly increased risk for VTE (OR=1.33, 95% CI 0.75-2.34; OR=1.31, 95% CI 0.40-4.28).

Conclusions: ALK rearrangements were shown to be associated with increased VTE risks in patients diagnosed with non-small lung cancer, while there was no significant relation observed between VTE risks and EGFR or KRAS mutations in lung cancer patients.

Keywords: ALK; EGFR; KRAS; ROS1; arterial thromboembolism (ATE); non-small-cell lung cancer; venous thromboembolism (VTE).

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Qian, Fu, Zheng, Zhou and Zhou.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Pooled estimates for incidence of VTE in patients with 4 driver gene types.
Figure 3
Figure 3
Forest plot demonstrating the association of driver genes with VTE events.
Figure 4
Figure 4
Subgroup analysis of VTE incidence in ALK rearranged patients. *Studies containing VTEs that occurred prior to diagnosis were also included; † Besides PE and DVT, venous thrombosis occurred at other sites were also included, including vena cava, neck vein, portal vein and other sites. No catheter-related events was included.
Figure 5
Figure 5
Subgroup analysis of VTE incidence in EGFR mutant patients. *Studies containing VTEs that occurred prior to diagnosis were also included.
Figure 6
Figure 6
The association of driver genes with PE events. (A) Pooled estimates for incidence of PE in patients with EGFR mutation, ALK rearrangement and ROS1 rearrangement. (B) Forest plot demonstrating the association of driver genes with PE events.
Figure 7
Figure 7
Pooled rate estimates for ATE in patients with ALK or ROS1 rearrangement.

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