Miliary metastases are associated with epidermal growth factor receptor mutations in non-small cell lung cancer: a population-based study

Abstract

Background: Miliary metastases are characterized by metastatic nodules that are diffuse, innumerable and small. The purpose of this study was to examine the incidence, prognostic significance and impact of epidermal growth factor receptor (EGFR) mutations for miliary metastases from non-small cell lung cancer (NSCLC).

Material and methods: Patients were identified from a Provincial cancer registry (British Columbia, Canada) for the period 2010-2012. Inclusion criteria were stage IV NSCLC at presentation and conclusive EGFR mutation testing. Miliary metastases were defined by subjective and objective radiographic criteria. The primary endpoint was the incidence of miliary lung, brain and liver metastases. Secondary endpoints were survival and the prognostic implication for each site of miliary metastases.

Results: For 543 patients, the total number of brain, lung and liver metastases were 165 (30.4%), 290 (53.4%) and 67 (12.3%), respectively. The EGFR mutation positive (EGFR+) subgroup had a significantly higher 3-year cumulative incidence of miliary brain (4.1 vs. 0.5%, p = .015) and miliary lung (11.6 vs. 3.3%, p < .001) metastases compared to EGFR wild type (WT). A greater proportion of metastases from EGFR + cancers were miliary for brain (8.5 vs. 1.7%, p = .035) and lung (18.9 vs. 6.9%, p = .003) sites. Only non-miliary brain (HR = 1.45) and liver (HR = 1.70) metastases predicted for poor overall survival.

Conclusions: Mutations in EGFR were associated with a higher rate of miliary brain and lung metastases. The presence of miliary metastases did not predict for poor overall survival.