Background 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 aimed to assess risk factors of BM and to define the highest-risk subset.Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan-Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM.Results 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 the ratio of metastatic to examined nodes or lymph node ratio (LNR) [greater than or equal to] 30% (RR: 3.33, 95% CI: 1.79-6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR [greater than or equal to] 30%, the 5-year actuarial risk of BM was 57.3%.Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR [greater than or equal to] 30% are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.
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