Outcomes of 27 Non-Small Cell Lung Cancer Patients Receiving Resections of Paired Primary Pulmonary and Brain Metastatic Tumours: Is EGFR Negative Mutation of Brain Metastasis Bring More Benefit?

Abstract Background: To analyze the heterogeneity and clinical outcomes of epidermal growth factor receptor (EGFR) gene mutation in primary tumour and corresponding brain metastasis(BM) in non-small cell lung cancer (NSCLC).Methods: Primary pulmonary tumours and paired metastatic brain tumours were surgically removed from twenty-seven NSCLC patients from July 1999 to November 2013 in our hospital. All brain lesions were confirmed as metastases stemming from NSCLC by pathological examination. EGFR gene (exons 18-21) mutant status was detected in matched tumour by using amplification refraction mutation system (ARMS). If inconsistency was detected, the paired tumour was evaluated again. The McNemar test was performed to compare the consistency of the paired tumour, and the Kappa test was used to quantify the agreement of both methods.Progression free survival(PFS) and overall survival(OS) were exhibited by the Kaplan-Meier.Results: In this study, of the 27 patients, nine (33.3%) cases were found to have EGFR mutations in BMs, and ten (37.0%) patients were detected positive EGFR status in primary lung tumour tissue. The rate of consistency of the matched tumour was 24/27 (88.9%, P≤0.001), and the Kappa coefficient was 0.757. Among the three cases presenting EGFR mutational heterogeneity, two patients harbored EGFR mutation in primary tumors but was negative in BMs, meanwhile, the other patient had the opposite pattern. Comparing to patients with consistent EGFR mutations(both mutant or wild),patients with inconsistent EGFR mutations tended to have better outcomes, including PFS(37.2months vs 25.0months vs 16.5months,P=0.159) and OS(53.6months vs 27.5months vs 26.8months,P=0.380), further analysis showed that two patients whose EGFR mutant-type primary tumor progressing to wild-type cerebral metastastic tumor might have longer overall survival(53.6months,37.8months) than one patient harboring reverse mutant difference(EGFR wild-type primary tumor progressing to mutant-type brain metastastic tumor) (16.7months). Also we found that patients with wild type in brain metastatic tumour had longer overall survival (OS)(mOS, 36.3 months vs 29.1months, P = 0.944).Conclusions: EGFR mutation status in NSCLC patients between primary lung tumour and paired BM was heterogeneous, patients harbored wild type EGFR mutation in BM might have better outcomes, especially for positive status transferred to wild.