ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events |
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Authors: | Terry L Ng Derek E Smith Rao Mushtaq Tejas Patil Anastasios Dimou Shuo Yang Qian Liu Xuefei Li Caicun Zhou Robert T Jones Megan M Tu Flora Yan I Alex Bowman Stephen V Liu Siera Newkirk Joshua Bauml Robert C Doebele Dara L Aisner D Ross Camidge |
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Institution: | 1. Division of Medical Oncology, University of Colorado, Aurora, Colorado;2. Department of Pediatrics, Cancer Center Biostatistics Core, University of Colorado and Children’s Hospital Colorado, Aurora, Colorado;3. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China;4. Department of Pharmacology, University of Colorado, Aurora, Colorado;5. Department of Surgery, University of Colorado, Denver, and University of Colorado Comprehensive Cancer Center, Aurora, Colorado;6. University of Texas at Southwestern, Dallas, Texas;7. Georgetown University, Washington, DC;8. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;9. University of Colorado, Department of Pathology, Aurora, Colorado |
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Abstract: | IntroductionThis study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate.MethodsVenous 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.ResultsEligible 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.ConclusionsThe 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. |
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Keywords: | Lung cancer Oncogene driver Thrombosis |
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