ROS1 gene rearrangements are associated with an elevated risk of peri-diagnosis thromboembolic events,Journal of Thoracic Oncology

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ROS1 gene rearrangements are associated with an elevated risk of peri-diagnosis thromboembolic events
Journal of Thoracic Oncology ( IF 21.0 ) Pub Date : 2019-04-01 , DOI: 10.1016/j.jtho.2018.12.001
Terry L Ng ₁ , Derek E Smith ₂ , Rao Mushtaq ₁ , Tejas Patil ₁ , Anastasios Dimou ₁ , Shuo Yang ₃ , Qian Liu ₃ , Xuefei Li ₃ , Caicun Zhou ₃ , Robert T Jones ₄ , Megan M Tu ₅ , Flora Yan ₆ , I Alex Bowman ₆ , Stephen V Liu ₇ , Siera Newkirk ₈ , Joshua Bauml ₈ , Robert C Doebele ₁ , Dara L Aisner ₉ , Dexiang Gao ₂ , Shengxiang Ren ₃ , D Ross Camidge ₁

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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.

更新日期：2019-04-01

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