Division of Medical Oncology, University of Colorado, Aurora, Colorado.
Department of Pediatrics, Cancer Center Biostatistics Core, University of Colorado and Children's Hospital Colorado, Aurora, Colorado.
J Thorac Oncol. 2019 Apr;14(4):596-605. doi: 10.1016/j.jtho.2018.12.001. Epub 2018 Dec 10.
INTRODUCTION: This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. METHODS: Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002-April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers. RESULTS: Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group. CONCLUSIONS: The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC.
简介:本研究旨在确定 ROS1 基因重排的晚期非小细胞肺癌(ROS1+ NSCLC)的血栓栓塞事件(TEE)发生率是否高于预期。
方法:在美国和中国的五家学术中心,在诊断为 ROS1+、ALK+、EGFR+或 KRAS+晚期 NSCLC 后±365 天内,捕获静脉和动脉 TEE(2002 年 10 月至 2018 年 4 月)。主要终点是在诊断后±90 天内,ROS1+与间变性淋巴瘤激酶(ALK+)、表皮生长因子受体(EGFR+)和 KRAS+ NSCLC 相比,TEE 的发生率。采用 logistic 回归评估肿瘤基因驱动因素之间 TEE 发生的几率是否不同。
结果:对 95 例 ROS1+、193 例 ALK+、300 例 EGFR+和 152 例 KRAS+ NSCLC 患者的合格数据进行了分析。TEE 的发生率分别为 34.7%(n=33)、22.3%(n=43)、13.7%(n=41)和 18.4%(n=28)。单因素分析显示,ROS1+ NSCLC 发生 TEE 的几率高于 ALK+、EGFR+和 KRAS+队列。多变量分析显示,与 EGFR+和 KRAS+队列相比,ROS1+发生 TEE 的几率显著更高,比值比(OR)为 2.44,95%置信区间为 1.31-4.57(p=0.005),OR:2.62,95%置信区间为 1.26-5.46(p=0.01)。虽然数值上更高,但与 ALK+相比,ROS1+发生 TEE 的几率无统计学意义(OR:1.45,p=0.229)。在整个研究队列或在每个分子组中,诊断后±90 天内有或没有 TEE 的患者的总生存没有显著差异。
结论:与 EGFR+和 KRAS+病例相比,ROS+晚期 NSCLC 患者发生围诊断性 TEE 的风险显著升高。ALK+ NSCLC 中 TEE 风险可能同样升高。
J Thorac Oncol. 2018-12-10
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