Risk Factors Of Brain Metastases In Non-small Cell Lung Cancer

First part Risk Factors of Brain Metastases in Completely Resected Pathological Stage ⅢA-N2Non-Small Cell Lung CancerObjective Brain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage ⅢA-N2(pⅢA-N2) NSCLC, we assess risk factors of BM and define the highest risk subset.Methods and Materials Between2003and2005, the records of217consecutive patients with pIIIA-N2NSCLC in our institution were reviewed. Failure pattern was analyzed. The cumulative incidence of BM was estimated by Kaplan-Meier method, and the differences between the groups were analyzed by log-rank test. Multivariate Cox regression analysis assessed risk factors of BM.Results Five-year overall survival of all patients was32.7%. Fifty-three (24.4%) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]:4.13,95%CI:1.86-9.19; P=0.001) and ratio of metastatic to examined nodes or lymph node ratio (LNR)≥30%(RR:3.33,95%CI:1.79-6.18; P=0.000) were associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR>30%, the5-year actuarial risk of BM was57.3%.Conclusions In NSCLC, patients with completely resected pIIIA-N2non-squamous cell cancer and LNR>30%are at the highest risk for BM, and most likely to benefit from PCI. Further trials on PCI should focus on the highest risk subset. Second part MicroRNA signature predicts brain metastases of lung adenocarcinomaObjective Brain metastases (BM) can affect25%of non-small cell lung cancer (NSCLC) patients during their lifetime, and it is one of the most common failures of locally advanced NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. We have discovered adenocarcinoma/adenosquamous cancer as clinical risk factor of BM, and about40%of patients with completely resected pathological stage IIIA-N2(pIIIA-N2) lung adenocarcinoma/adenosquamous cancer developed BM。MicroRNA regulates the expression of target mRNAs. MicroRNA plays a role in regulating a variety of targets and, consequently, multiple pathways, which make it a powerful tool for early detection of disease, risk assessment, and prognosis. We aimed to investigate microRNAs that may serve as biomarkers to differentiate between lung adenocarcinoma patients with and without BM.Methods Between2003and2005, the records of patients with pIIIA-N2lung adenocarcinoma/adenosquamous cancer in our institution were reviewed. Eighty-seven patients were recruited, and32of them developed BM. MicroRNA microarray profiling was performed on tumor tissues from clinically matched patients with and without BM. Cox regression analysis was applied to assess the association between microRNA and risk of BM.Results Six microRNAs were found to be significantly differentially expressed in lung adenocarcinoma tissues between patients with and without BM, five of which were up regulated and the rest was down regulated in patients with BM. Moreover, levels of the6microRNAs were significantly associated with risk of BM. The six-micro RNA signature also was an independent predictor of risk of BM.Conclusions MicroRNAs may serve as biomarkers to distinguish lung adenocarcinoma patients at higher risk of BM. With further validation in additional independent cohorts and mechanism study, these miRNAs may be incorporated into clinical treatment decision making to stratify NSCLC patients most likely to benefit from PCI or intensive magnetic resonance imaging (MRI).