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

Pascale Tomasini (1, 2) , Cindy Serdjebi (1, 3) , Nataliya Khobta (1) , Philippe Metellus (4) , L'Houcine Ouafik (2, 3) , Isabelle Nanni (3) , Laurent Greillier (1, 2) , Anderson Loundou (5) , Frederic Fina (3) , Celine Mascaux (1, 2) , Fabrice Barlesi (1, 2)

1 Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
2 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
3 Laboratoire de Transfert en Oncologie Biologique
4 Service de neurochirurgie
5 SPMC - Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants

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.

Keywords: brain metastasis; lung neoplasm; KRAS; EGFR; incidence; recurrence; survival

Domains: Life Sciences [q-bio]; Cancer

Pascale Tomasini, Cindy Serdjebi, Nataliya Khobta, Philippe Metellus, L'Houcine Ouafik, et al.. EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer. International Journal of Molecular Sciences, 2016, 17 (12), pp.2132. ⟨10.3390/ijms17122132⟩. ⟨hal-01477442⟩