The Association Between Thromboembolic Events and ALK, ROS1, RET Rearrangements or EGFR Mutations in Patients With Advanced Lung Adenocarcinoma: A Retrospective Cohort Study.

Introduction: Previous studies have reported inconsistent findings regarding the associationbetween ALK and ROS1 rearrangements in lung cancer and thromboembolic risk. This retrospective study aimed to investigate this association in advanced lung adenocarcinoma patients with ALK, ROS1, RET rearrangements, and EGFR mutations.

Materials and methods: We retrospectively collected information on patients with advanced lung adenocarcinoma in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2013 to March 2021. All patients with confirmed ALK, ROS1, or RET rearrangements, as well as a comparison cohort of those with EGFR mutation, were included. Clinical characteristics were analyzed, and the association between driver genes and TE risks was analyzed using competing risk and logistic regression.

Results: A total of 546 patients were included in the study. Among them, those with ROS1 rearrangements exhibited the highest cumulative incidence of thromboembolic events (TEs), reaching 17.5% ± 0.2% during the peri-diagnostic period (within 6 months following diagnosis). Regardless of the entire follow-up or the peri-diagnostic period, ROS1 rearrangements were significantly associated with an increased risk of TEs. Multivariate analysis revealed ROS1 rearrangements, the number of comorbidities, the size of mediastinal lymph nodes, and elevated C-reactive protein (CRP) levels as TE risk factors during the peri-diagnostic period. Throughout the follow-up period, ROS1 rearrangements and hypertension were independent TE risk factors. In addition, the development of TE significantly affected the overall survival of patients with EGFR mutations.

Conclusion: ROS1 rearrangements were significantly associated with an increased risk of TE.