Common genetic driver mutation in NSCLC and their association with thromboembolic events: A retrospective study

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2022-10, Vol.172, p.29-34
• Main Authors: Lin, Miaozhen, Lu, Yujuan, Yu, Qiwen, Chen, Zebin, Peng, Jiayu, Cai, Xiuyu
• Format: Article
• Language: English
• Subjects: ALK; Epidermal growth factor receptor (EGFR); Gene mutation; KRAS; Lung cancer; Non-small cell lung carcinoma; Risk factor; ROS; Thromboembolism; Thrombosis
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2022.06.011

•Non-small cell lung cancer patients with different genetic mutations may have different risks of thrombosis.•The presence of ALK/ROS rearrangements is significantly associated with an increase in thrombosis risk in NSCLC patients, compared to other common gene mutation status.•Based on the result of our study, for patients who are treated with ALK/ROS TKI, the risk of TE might increase additionally.•Identifying patients at high risk of TE will allow a more personalized approach and benefit more from the use of pharmacologic thromboprophylaxis. This retrospective study aimed to estimate the incidence, risk factors of thromboembolism events (TEs) in non-small cell lung cancer patients harboring common gene mutation, and evaluate a genetic link between oncogenes and the risk of TEs in Asian patients with NSCLC. Univariate and multivariate Cox’s proportional hazards regression models were used to identify the strongest predictors of TE development and evaluate the risk of TE in patients with different gene statuses of NSCLC patients. In univariate and multivariate COX analysis, patient with squamous cell carcinoma (HR 3.01, 95% CI: [1.06,8.56]; p = 0.039), multi-site metastases (HR: 2.72; 95% CI: [1.08,6.92]; p = 0.032) or high white blood cell (WBC) (HR 3.24, 95% CI: [1.46,7.22]; p = 0.004), less hemoglobin (HGB) (HR 4.89, 95% CI: [1.90,12.64]; p = 0.001), are at higher risk of thrombosis. At the molecular level, ROS and ALK rearrangement is highly associated with TE development, with HR of 4.04 (95%CI: [1.54,10.58]; p = 0.005) and HR of 3.57 (95% CI: [1.01,12.66]; p = 0.049) in univariate analysis, and even higher in multivariate analysis. EGFR mutations seem to be a protective factor against TE in univariate analyses (HR:0.28, 95%CI [0.12,0.65], p = 0.003) but are not statistically significant in the multivariate model. No correlation between KRAS mutations and TE events in both models. Besides, a numerically higher cumulative incidence of thrombosis event was observed in patients who used TKI (HR 1.473; 95% CI: [0.682, 3.181]; p = 0.32). Our study demonstrated that driver gene mutation may increase the risk of thrombosis in non-small cell lung cancer patients. The presence of ALK/ROS rearrangements in our study is associated with an approximately threefold to fourfold increase in thrombosis risk in NSCLC patients. For advanced-stage patients who used TKI, an increased incidence of thrombosis risk and shorter follow-up were observed.