Clinical characteristics and their influences on the survival of leptomeningeal metastasis derived from lung adenocarcinoma harboring epithelial growth factor receptor mutation

Abstract

Objective: To analyze the clinical characteristics of leptomeningeal metastasis (LM) patients from epithelial growth factor receptor (EGFR)-mutated lung adenocarcinoma, and their impacts on the survival of the patients. Methods: From July 2018 to July 2022, the clinicopathological data of 81 patients diagnosed as EGFR-mutated lung adenocarcinoma LM by cytopathology who admitted to the Department of Oncology of Xiangya Hospital of Central South University were retrospectively analyzed, including 33 males and 48 females. The age ranged from 31 to 76 years, with a median age of 54 years. All the 81 patients were followed up, with a median follow-up of 21.0 months (95%CI: 12.5 to 29.5 months). The Kaplan Meier method was used to draw survival curve. Cox proportional hazards regression model was used to analyze the impact of the factors on the survival of patients. Results: Among the 81 patients, the interval between the initial diagnosis of lung cancer and the pathological diagnosis of LM in cerebrospinal fluid (CSF) was 0-108 months, with a median interval of 14 months. Fifty-two patients (64.2%) used the third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), while 17 patients (21.0%) used EGFR-TKIs in combination with other drugs, and 12 patients (14.8%) were treated with best supportive care (BSC). Sixty patients (74.1%) had a Kanofsky performance status (KPS) score of less than 60 points, and 71 patients (87.7%) had brain parenchymal metastasis and/or spinal metastasis. Twenty-two patients (27.2%) used pemetrexed through intrathecal CSF, and 17 patients (21.0%) used pemetrexed through the Ommaya sac to the CSF of the ventricle. The incidence of adverse event related to the administration of pemetrexed through CSF was 64.1% (25/39), mainly manifested as myelosuppression, including 22 patients of leukocyte reduction, 25 patients of hemoglobin reduction, and 14 patients of platelet reduction. The median post-leptomeningeal metastasis overall survival (pLM-OS) in 81 patients was 11.0 (95%CI: 7.7-14.3) months. KPS score≥60 points (HR=0.407, 95%CI: 0.170-0.973, P=0.043), CSF cytology negative after treatment (vs persistent positive, HR=0.351, 95%CI: 0.155-0.792, P=0.012), intraventricular administration of pemetrexed (vs non intraventricular administration of pemetrexed, HR=0.319, 95%CI: 0.137-0.745, P=0.008) and the treatment with third-generation EGFR-TKIs after LM (vs EGFR-TKIs in combination with other drugs, HR=0.486, 95%CI: 0.237-0.998, P=0.049) were a factor affecting pLM-OS of patients. Conclusions: Brain parenchyma, or/and spine are the most sites where the LM patients concurrently metastasize. KPS score≥60 points and CSF cytology negative after treatment, intraventricular administration of pemetrexed and the treatment with third-generation EGFR-TKIs are indictors affecting pLM-OS of the patients.