# Antiplatelet Therapy Mitigates Brain Metastasis Risk in Non-Small Cell Lung Cancer: Insights from a Comprehensive Retrospective Study

## TL;DR

This study finds that medications used to prevent blood clots may reduce the risk of lung cancer spreading to the brain, especially in advanced cases.

## Contribution

The study is one of the first to show in real-world data that antiplatelet therapy is associated with reduced brain metastasis risk in non-small cell lung cancer.

## Key findings

- Patients on antiplatelet therapy had a significantly lower risk of developing brain metastases (6.9% vs. 20.0%).
- Antiplatelet users had longer time to metastasis development (77.5 vs. 62.6 months).
- No brain metastases occurred in patients who started antiplatelet therapy shortly after diagnosis.

## Abstract

People with lung cancer often face a serious complication: the spread of cancer to the brain. This condition greatly worsens quality of life and survival. In this study, we looked at data from 650 people with lung cancer to see if taking medications that reduce blood clotting—commonly used to prevent heart attacks or strokes—might also lower the risk of brain cancer spread. These medications, mainly aspirin, were more often used by older patients with other health issues. Still, we found that those who took them had a lower chance of developing brain cancer spread during their illness. This effect was even stronger in people with more advanced lung cancer. Those on these medications also lived longer without their cancer getting worse. Notably, none of the people who started these medications shortly after their cancer diagnosis developed brain cancer spread. Our results suggest that these common medications may help slow or prevent the spread of lung cancer to the brain. If confirmed by future studies, this could lead to new ways to improve outcomes for people with lung cancer using safe, widely available treatments.

Background: Brain metastases are a common and devastating complication of non-small cell lung cancer (NSCLC), severely affecting prognosis and quality of life. Despite increasing interest in the role of platelets in tumor progression and dissemination, the potential impact of antiplatelet therapy on brain metastasis in NSCLC remains underexplored. Methods: In this retrospective observational study, we analyzed data from 650 patients diagnosed with NSCLC over a four-year period to evaluate whether prior or subsequent exposure to antiplatelet agents correlates with a reduced incidence of brain metastases. Results: Patients exposed to antiplatelet therapy, predominantly aspirin, presented with more comorbidities and were generally older. Despite these differences, they showed a significantly lower risk of developing brain metastases during the disease course (6.9% vs. 20.0%, p < 0.001), particularly among those with advanced-stage disease at diagnosis. A longer time to metastasis development was also observed in antiplatelet users (77.5 vs. 62.6 months, p < 0.001), along with improved progression-free survival. Additionally, patients on antiplatelets before diagnosis had a lower probability of presenting brain metastases at the time of diagnosis (3.9% vs. 12.1%, p = 0.014), and no cases of brain metastases occurred in patients who started antiplatelet therapy shortly after diagnosis. These findings highlight the potential of antiplatelet agents to interfere with key mechanisms of metastatic spread, including immune evasion and premetastatic niche formation. Conclusions: Importantly, this study provides one of the first real-world analyses suggesting a consistent and stage-dependent association between antiplatelet use and reduced brain metastatic burden in NSCLC. By bridging the gap between preclinical insights and clinical outcomes, our work offers a novel and clinically relevant perspective that supports further research into the integration of antiplatelet therapy in NSCLC management.