After adjusting covariables, EGFR mutations were associated with BM in never-smokers (adjusted OR = 2.07, 95% CI = 1.02-4.34) and K-RAS mutations were risk factors for BM in males (adjusted OR = 3.86, 95% CI = 1.01-14.43).
Regarding molecular factors, all driver mutations in lung adenocarcinoma had a favorable effect (EGFR, HR 0.53, 95%CI 0.31-0.89; ALK, HR 0.28, 95%CI 0.12-0.66; KRAS, HR 0.65, 95%CI 0.47-0.92), triple negative status predicted poor prognosis in breast adenocarcinoma (HR 2.04, 95%CI 1.13-3.69), while no effect of BRAF/NRAS mutations was demonstrated in melanoma BMs.
Kaplan Meier analysis showed that clinical stage and brain metastasis were significantly associated with OS (both P<0.05), but neither KRAS exon 3 mutation nor PTEN exon 7 mutation was significantly associated with OS (P>0.05).
In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.
In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.
We retrospectively reviewed 1971 non-small-cell lung cancer files of patients with EGFR and KRAS testing and focused on 157 patients who had undergone RT for brain metastasis.
So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases.
KRAS-mutant NSCLC patients with concurrent LKB1 loss had a higher number of metastatic sites at the time of diagnosis (median 2.5 vs. 2, P = 0.01), higher incidence of extrathoracic metastases (P = 0.01), and developed brain metastasis more frequently (48% vs. 25%, P = 0.02).
Presence of KRAS mutations was associated with positive smoking history (p=0.015, Chi square test) and presence of EGFR mutation correlated with unfavourable overall survival time from BM diagnosis (p=0.019, log rank test).
We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC).
Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases.
In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC.
In the case of comorbidity of disorders in the ALK (uncertain prognostic significance) and KRAS gene (described as unfavorable prognostic factor), these abnormalities may ultimately decide the course of the disease in the form of brain metastases.