The EGFR-rearranged adenocarcinoma is associated with a high rate of venous thromboembolism

Abstract

Background: The purpose of this study was to investigate the incidence of venous thromboembolism (VTE) in epidermal growth factor receptor (EGFR) mutations patients with lung adenocarcinoma, to provide clinical basis for the perioperative prevention and treatment of VTE in patients with lung cancer.

Methods: This study included patients with invasive lung adenocarcinoma confirmed by pathology from July 2016 to March 2018 after surgical pulmonectomy in Thoracic Surgery Department of Beijing Chaoyang Hospital. All enrolled patients were tested for relevant gene mutations. All patients were classified as adenocarcinoma subtypes by the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). Patients were divided into the VTE group and the control group according to whether VTE occurred postoperatively. Baseline data, gene test results, operative data and tumor pathology data between the two groups were compared.

Results: According to the inclusion criteria, a total of 323 patients underwent lung cancer surgery were analyzed in this study, including 148 males and 175 females, aged from 25 to 82 years old. Postoperative VTE occurred in 33 patients, with an incidence of 10.2%. Compared the baseline data, there were significant differences in age and BMI between the two groups, but no significant differences in other indicators. Comparing the results of postoperative genetic tests, the cases of exon 18, 19, 20, 21, 30, 31 mutation, exon 18 and 20 mixed mutation and exon 20 and 21 mixed mutation were 5, 42, 6, 57, 1, 3, 1 and 1. The total EGFR mutation rate in the enrolled patients was 36.2% (117/323). Among them, the proportion of EGFR mutation in the VTE group was significantly higher than that in the non-VTE group (60.6% vs. 33.4%, P=0.002). Exon mutations in specific regions and mixed region of EGFR were not statistically significant between them; there was no statistical difference in the concomitant KRAS and ALK gene mutations between them. Comparing the pathological conditions, the proportion of acinar dominant lung adenocarcinoma in the VTE group was higher than that in the non-VTE group (57.6% vs. 30.7%, P=0.002); other histologic subtypes showed no statistical difference. The D-dimer difference before and 1 day after surgery, preoperative FEV1, surgical method, duration of surgery and blood loss were statistically significant differences between the two groups. The results of univariate analysis showed that there were significant differences between the VTE group and the control group in proportion of EGFR mutant lung adenocarcinoma, age, BMI, D-dimer difference before and 1 day after surgery, preoperative FEV1, surgical method, duration of surgery, blood loss and proportion of acinar dominant lung adenocarcinoma (P<0.05). However, VTE was not significantly correlated with gender, ALK or KRAS gene mutation and other factors. Multi-factor logistics regression analysis shows that Patients with EGFR gene mutation infiltrating lung adenocarcinoma, acinar dominant lung adenocarcinoma, FEV1 and difference of D-dimer (d1-pre) are independent risk factors for postoperative lung cancer complicated with VTE.

Conclusions: The incidence of VTE was 10.2% in patients with invasive lung adenocarcinoma without prophylactic anticoagulant therapy. EGFR gene mutation is an independent risk factor for postoperative VTE in lung cancer, and the incidence of VTE in adenocarcinoma with alveolar predominance is the highest. Other independent risk factors included the difference of D-dimer (d1-pre) and preoperative FEV1.

Keywords: Venous thromboembolism (VTE); adenocarcinoma with alveolar predominance; epidermal growth factor receptor mutant lung adenocarcinoma; thoracic surgery.

Figure 1

Screening flow chart.