Abstract
BackgroundLeptomeningeal metastasis (LM) is a detrimental complication of advanced non‐small‐cell lung cancer (NSCLC), and the optimal therapeutic approach for LM patients is in shortage. This retrospective study aimed to investigate the clinical features and prognostic factors of NSCLC patients with LM.MethodsWe retrospectively reviewed the medical records of NSCLC patients with LM at the Shandong Cancer Hospital and Institute between July 2014 and March 2018. Identified cases had pathology‐proven NSCLC with either positive cerebrospinal fluid cytology or leptomeningeal enhancement by MRI.ResultsOne hundred and thirty‐six NSCLC patients (58 men, 78 women) with LM were enrolled in the retrospective study; median age was 55 years (range, 29‐89 years). Fifty‐one patients harbored EGFR mutations, ALK rearrangement was detected in 6 patients. Treatment for LM consisted of EGFR‐TKIs alone in 11 patients, whole brain radiotherapy (WBRT) alone in 19 patients, Chemotherapy (ChT) alone in 12 patients, EGFR‐TKIs plus WBRT in 30 patients, WBRT plus ChT in 25 patients, and EGFR‐TKIs plus ChT in 24 patients. The median progression‐free survival was 3.9 months (95% confidence interval [CI]: 3.178‐4.622), and the median overall survival (OSLM) was 9.8 months (95% CI:7.5‐12.1). Thirty patients who received WBRT plus EGFR‐TKIs achieved longer survival than those who only received WBRT (median 13.6 vs 8.8 months; P = 0.027), but did not add any survival benefit than those only received EGFR‐TKIs (median 13.6 vs 13.9 months; P = 0.352). A multivariate analysis indicated that KPS ≥ 80 (hazard ratio [HR] = 0.592, 95% CI:0.369‐0.95; P = 0.03) and EGFR‐TKIs (HR = 0.507, 95% CI:0.283‐0.908; P = 0.022) after LM diagnosis were independent favourable predictors of survival, whereas smoking (HR = 1.181, 95% CI:1.009‐3.246; P = 0.047) was an independent predictor of poor survival.ConclusionsOur results suggest that patients with good performance statuses, non‐smoking patients, and the administration of EGFR‐TKIs might improve clinical outcomes in NSCLC patients with LM.
Highlights
Leptomeningeal metastasis (LM), or leptomeningeal carcinomatosis, is a devastating metastatic complication of systemic cancer that arises from the spread of malignant cells spread to the leptomeninges, subarachnoid space, and cerebrospinal fluid (CSF) compartments.[1-6]
Multivariate analysis indicated that Karnofsky performance status (KPS) ≥ 80 (HR = 0.592, 95% confidence interval (CI): 0.369‐0.95; P = 0.03) and the application of epidermal growth factor receptor (EGFR)‐ tyrosine kinase inhibitor (TKI) (HR = 0.507, 95% CI:0.283‐0.908; P = 0.022) were statistically significant factors associated with a favorable survival, whereas smoking (HR = 1.181, 95% CI: 1.009‐3.246; P = 0.047) was an independent predictor of poor survival
In the application of systemic treatment, including systemic ChT and EGFR‐TKIs, only EGFR‐ TKIs was identified as an independent prognostic factor in the current analysis, which was consistent with findings from several previous studies.[10,13,14,16,17]
Summary
Leptomeningeal metastasis (LM), or leptomeningeal carcinomatosis, is a devastating metastatic complication of systemic cancer that arises from the spread of malignant cells spread to the leptomeninges (pia and arachnoid mater), subarachnoid space, and cerebrospinal fluid (CSF) compartments.[1-6]. Optimal treatment modalities for LM in NSCLC patients remains poorly defined. NSCLC patients with cytologically or radiographically proven LM were collected at the Shandong Cancer Hospital and Institute between July 2014 and March 2018. A diagnosis of LM was defined as positive CSF cytology (malignant cells) and/or focal or diffuse enhancement of leptomeninges, cranial nerves, and spinal cord diagnosed by brain and spine MRI. The medical records of these patients included their demographic data, clinical characteristics, tumor‐related features, treatment modalities, and clinical outcomes. Tumor‐related features comprised NSCLC histological types, EGFR/ALK mutation status, treatments before the diagnosis of LM (including EGFR‐TKIs and WBRT), the presence of prior or concurrent brain or spinal metastases at LM diagnosis, gadolinium‐enhanced MRI findings, CSF cytological results, date of LM diagnosis, and date of death or last follow‐up. Analyses were conducted by using the SPSS Statistics version 20 (IBM Corporation, NY)
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