Association of Venous Thromboembolism and Early Mortality in Patients with Newly Diagnosed Metastatic Non-Small Cell Lung Cancer

Yanping Su,1 Meirong Huo,1 Lin Hua,2 Yuan Zhang,1 Jiawen Yi,1 Shu Zhang,1 Jie Li,1 Yuhui Zhang1 1Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, Beijing, People’s Republic of China; 2School of Biomedical Engineering, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Yuhui ZhangDepartment of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, 8 Gongtinan Road, Chaoyang District, Beijing, People’s Republic of ChinaTel +86 13520208369Email zhangyhcy@163.comPurpose: To explore the relationship between venous thromboembolism (VTE) and early mortality (within six months) in Chinese patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) after entering the era of precision treatment.Methods: A cohort of 706 consecutive subjects with newly diagnosed metastatic NSCLC were prospectively observed. Clinical and survival data were recorded over a six-month follow-up period. The predictive factors for the occurrence of VTE and the relationship with early mortality were evaluated through univariate and multivariate analyses.Results: During the six-month follow-up period, VTE events occurred in 12.2% (86/706) of the enrolled patients. In the multivariate analyses for VTE, an age older than 70 years (vs < 70: sub-distribution hazard radio [SHR], 1.678; 95% confidence interval (CI), 1.073– 2.600; P=0.022), an Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0/1: SHR, 1.946; 95% CI, 1.277– 2.970; P=0.002), and having an ALK rearrangement (vs non-rearrangement: SHR, 2.377; 95% CI, 1.186– 4.760; P=0.015) were significantly associated with the occurrence of VTE. Within six months, 116 subjects (16.4%) died, and the occurrence of VTE (vs no VTE: adjusted HR: 1.863; 95% CI: 1.178– 2.947, P=0.008) was remarkably associated with early mortality. Further analysis showed 98 patients (13.9%) with early mortality had EGFR/ALK wild-type genes, with a risk of early mortality 5.935-fold higher than that of patients with an EGFR mutation/ALK rearrangement. Finally, subgroup analyses showed that VTE occurrence was a significant factor for predicting early mortality in patients with EGFR/ALK wild-type genes (adjusted HR: 1.682; 95% CI: 1.023– 2.768, P=0.041).Conclusion: Patients with an EGFR mutation/ALK rearrangement had a significantly decreased risk of early mortality in the era of targeted therapy; however, VTE occurrence remained an important predictor for early mortality in metastatic NSCLC patients, especially in patients with EGFR/ALK wild-type genes.Keywords: venous thromboembolism, non-small cell lung cancer, early mortality