Department of VIP Inpatient, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China.
Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou China.
Lung Cancer. 2022 Oct;172:29-34. doi: 10.1016/j.lungcan.2022.06.011. Epub 2022 Jun 22.
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.
本回顾性研究旨在估计携带常见基因突变的非小细胞肺癌患者发生血栓栓塞事件（TE）的发生率、风险因素，并评估亚洲非小细胞肺癌患者中致癌基因与 TE 风险之间的遗传联系。
采用单变量和多变量 Cox 比例风险回归模型来确定 TE 发展的最强预测因素，并评估不同基因状态的 NSCLC 患者发生 TE 的风险。
在单变量和多变量 COX 分析中，鳞状细胞癌患者（HR 3.01，95%CI：[1.06,8.56]；p=0.039）、多部位转移（HR：2.72；95%CI：[1.08,6.92]；p=0.032）或高白细胞（WBC）（HR 3.24，95%CI：[1.46,7.22]；p=0.004）、较低的血红蛋白（HGB）（HR 4.89，95%CI：[1.90,12.64]；p=0.001）的患者发生血栓的风险更高。在分子水平上，ROS 和 ALK 重排与 TE 发展高度相关，单变量分析的 HR 为 4.04（95%CI：[1.54,10.58]；p=0.005）和 HR 为 3.57（95%CI：[1.01,12.66]；p=0.049），多变量分析时更高。在单变量分析中，EGFR 突变似乎是 TE 的保护因素（HR：0.28，95%CI [0.12,0.65]，p=0.003），但在多变量模型中无统计学意义。在两种模型中，KRAS 突变与 TE 事件之间均无相关性。此外，与未使用 TKI 的患者相比，使用 TKI 的患者的血栓事件累积发生率更高（HR 1.473；95%CI：[0.682, 3.181]；p=0.32）。
本研究表明，驱动基因突变可能会增加非小细胞肺癌患者发生血栓的风险。本研究中 ALK/ROS 重排与 NSCLC 患者血栓风险增加约 3 至 4 倍相关。对于使用 TKI 的晚期患者，观察到血栓风险增加和随访时间缩短。
