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Int. J. Mol. Sci. 2016, 17(12), 2132; doi:10.3390/ijms17122132

EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

1
Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France
2
Inserm U911 CRO2 (Centre de Recherche en Oncologie biologique et Onco-pharmacologie), Aix Marseille University, Marseille 13005, France
3
Assistance Publique Hôpitaux de Marseille, Transfer Oncology Laboratory, Aix Marseille University, Marseille 13015, France
4
Department of Neurosurgery, Aix-Marseille University, Marseille 13005, France
5
Statistics Department, Aix Marseille University, Marseille 13005, France
*
Author to whom correspondence should be addressed.
Academic Editor: Dario Marchetti
Received: 28 September 2016 / Revised: 6 December 2016 / Accepted: 7 December 2016 / Published: 18 December 2016
(This article belongs to the Special Issue Brain Metastasis 2016)
View Full-Text   |   Download PDF [234 KB, uploaded 21 December 2016]   |  

Abstract

Background: Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients’ outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian) were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA) (Odds ratio OR = 8.745 [1.743–43.881], p = 0.008). Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078–0.699], p = 0.009). Among patients with untreated BM, overall survival (OS) was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240–41.012], p = 0.028), but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM. View Full-Text
Keywords: brain metastasis; lung neoplasm; KRAS; EGFR; incidence; recurrence; survival brain metastasis; lung neoplasm; KRAS; EGFR; incidence; recurrence; survival
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Tomasini, P.; Serdjebi, C.; Khobta, N.; Metellus, P.; Ouafik, L.; Nanni, I.; Greillier, L.; Loundou, A.; Fina, F.; Mascaux, C.; Barlesi, F. EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer. Int. J. Mol. Sci. 2016, 17, 2132.

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