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

## TL;DR

This study found that patients with ROS1 gene rearrangements in lung cancer have a higher risk of blood clots, especially around the time of diagnosis.

## Contribution

The study identifies ROS1 rearrangements as a novel risk factor for thromboembolic events in lung adenocarcinoma patients.

## Key findings

- ROS1 rearrangements were significantly associated with increased thromboembolic event risk.
- Thromboembolic events occurred most frequently during the peri-diagnostic period in ROS1-positive patients.
- Multiple comorbidities and elevated CRP levels were additional risk factors for thromboembolic events.

## Abstract

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.

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.

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.

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

In this retrospective study of 546 lung adenocarcinoma patients with four different driver genes, ROS1 rearrangements were associated with the increased risk of thromboembolic events (TEs), particularly during the peri‐diagnostic period (6 months before and after diagnosis). Risk factors of TEs during the peri‐diagnostic period included ROS1 rearrangements, multiple comorbidities, enlarged mediastinal lymph nodes, and elevated CRP levels.