Carcinomatous meningitis and <i>EGFR</i> mutation

Abstract

Background: Carcinomatous meningitis (CM) in non-small cell lung cancer (NSCLC) has no standard treatment and poor prognosis, with a median survival of 4-9 weeks. Recently, NSCLC subgroups with driver mutations were identified, with mutation of epidermal growth factor receptor gene (EGFR) being the most frequent. This retrospective study investigated the frequency and characteristics of CM in EGFR-mutated patients. Methods: From April 2007 to June 2013, consecutive NSCLC patients were screened for EGFR mutations using the PNA-LNA PCR Clamp in one institution. Diagnosis of CM was based on the presence of malignant cells in cerebrospinal fluid and/or MRI detection of leptomeningeal enhancement. Incidence and clinical features of CM patients were investigated from medical records. Results: Of 1343 NSCLC patients, 387 (28.8%) harboring EGFR mutations. Thirty-five patients (2.6%) developed CM; the rate of CM in EGFR-mutated patients (25/387, 6.46%) was significantly higher than in patients lacking the mutations (10/956, 1.04%; p < 0.01). Multiplex logistic analysis indicated strong associations between CM and EGFR mutation (p < 0.0001), brain metastasis (p < 0.0001) and non-squamous cell carcinoma histology (p = 0.026). Conclusions: NSCLC patients with EGFR mutations are more likely to develop CM than those with wild EGFR.