BackgroundThe brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methodsWe retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.ResultsOut of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.ConclusionsExcept for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.
Copyright: Xiong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Objectives: Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. Patients and methods: Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study. EGFR mutations including L858R, exon 19 deletion (19-del) and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples. Results: We observed a significant reduction in plasma EGFR mutation abundance during the first two-month of TKI treatment. Acquiring of secondary T790M gatekeeper mutation or completed "loss" of EGFR mutations represented two major categories of resistance profiles. Moreover, we demonstrated that levels of plasma EGFR mutations highly correlated with changes of tumor diameter as determined by radiographic imaging, or development of new lesions. In a subset of patients, we further showed that reappearance of EGFR mutations could be detected in plasma up to 5 months ahead of progressive disease (PD), suggesting an early detection of drug resistance. Conclusions: Our findings suggest that genomic analysis using plasma cfDNA may offer an effective approach to monitor clinical response and emergence of resistance.
S131study started in January 2012 and included pts who started treatment with gefitinib prior to study entry or at study entry (referred to as 'new pts'). Efficacy, safety and quality of life with gefitinib were assessed over a two-year follow up period. Results: A total of 361 pts were recruited across 104 sites up to March 2013, including 116 (32%) 'new' pts. Pt characteristics are presented in the table. Objective response rate (ORR), based on clinician assessment, was 66.8% (95% confidence interval [CI] 60.3; 70.3) in the overall population and 68.8% (95% CI 59.1; 76.7) in 'new' pts. Median duration of follow up was 20.6 months. Median progression-free survival (PFS) was 11.1 months (95% [CI 10.0, 11.9) in the overall population and 10.0 months (95% CI 7.7, 11.8) for 'new' pts. Median overall survival (OS) from initiation of gefitinib was 24.6 months (95% CI 21.4, 26.7) and 24.0 months (95% CI 20.5, 27.5) in the overall population and 'new' pts, respectively. Most frequently reported treatment-related adverse events were skin (24.6%) and GI (19.6%) disorders.
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