Abstract OBJECTIVE The most common solid systemic malignancies that metastasize to the leptomeninges are lung cancer, especially non-small cell lung cancer (NSCLC). Generally, patients develop leptomeningeal metastasis (LM) subsequent to brain parenchymal metastases (BM). However, its predictors remain unknown. Hence, the present study was carried out to explore the predictors of LM in brain metastatic NSCLC patients. METHODS The final analysis included 112 pathologically definite NSCLC patients with BMs treated in our center between July 1, 2014, and December 30, 2020. Of 112, one-half had LM. Three radiologists analyzed radiologic images independently. Anatomic proximity of BMs to the CSF space (dural-based metastases, periventricular or major CSF cisterns such as basal cisterns and cisterna magna) was measured and stratified into CSF space invading/bordering and detached lesions. The endpoint was the occurrence of LM or death, whichever occurred first. Univariable and multivariable logistic regressions were performed to identify potential predictors for LM. RESULTS Of 112, 48 (42.8%) were males, and 64 (57.2%) were females. Most patients (90.2%) had adenocarcinoma histology. The median follow-up time was 10.1 months (IQR, 4.2-18.4 months) following BM diagnosis. Univariate logistic regression analysis demonstrated that histology (OR 0.084, 95%CI 0.004-0.461, P=0.020), EGFR/ALK/ROS1 mutation (OR 3.868, 95%CI 1.583-10.079, P=0.003), CSF space invading/bordering lesion (OR 10.278, 95%CI 4.203-27.375, P=0.000), extracranial metastasis control (OR 2.7, 95%CI 1.191-6.309, P=0.019), upfront stereotactic radiosurgery (SRS) (OR 0.024, 95%CI 0.001-0.12, P=0.000), and target therapy (OR 4.476, 95%CI 1.877-11.464, P=0.001) were the potential predictor. CSF space invading/bordering lesion (OR 7.443, 95%CI 2.099-32.853, P=0.003) and upfront SRS (OR 0.035, 95%CI 0.002-0.212, P=0.003) remained statistically significant in the multivariate logistic regression analysis. CONCLUSION CSF space invading/bordering BMs may increase the risk of LM development in brain metastatic NSCLC patients, while upfront SRS targeting BM potentially decreases the risk. A prospective study is warranted to affirm.
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