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

Pascale Tomasini,Cindy Serdjebi,Isabelle Nanni,Nataliya Khobta,Laurent Greillier,Philippe Metellus,Frederic Fina,Anderson Loundou,L’Houcine Ouafik,Fabrice Barlesi,Celine Mascaux

doi:10.3390/ijms17122132

Pascale Tomasini, Cindy Serdjebi + Show 9 more

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https://doi.org/10.3390/ijms17122132

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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.

Highlights

Lung cancer remains the leading cause of cancer-related deaths worldwide [1]
Data from a total of 144 patients tested for EGFR and KRAS mutations between January 2009 and December 2010 at Multidisciplinary Oncology and Therapeutic Innovations department (MOTI) were obtained
Despite the lower brain metastases (BM) incidence and the better control of BM after local treatment in the KRAS-mutant group, these patients had a shorter overall survival. This suggests that the poor prognosis of KRAS-mutant non-small cell lung cancer (NSCLC) does not rely on BM

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Introduction

Lung cancer remains the leading cause of cancer-related deaths worldwide [1]. It is the leading cause of brain metastases (BM), accounting for 40% to 50% of all BM [2]. The median overall survival (OS) of lung cancer patients with BM is four to 11 weeks [4] Local treatments such as neurosurgery, stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) improve local control and are associated with increased median OS of up to 14 months [5]. 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. 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

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