Brain metastases are a common occurrence and a major cause of mortality in non-small-cell lung cancer, with few systemic treatment options. Although targeting epidermal growth factor receptor-associated tyrosine kinase with erlotinib and gefitinib results in durable responses in some patients, the activity of these drugs against brain metastases has been poorly documented. In particular, few reports have so far reported the activity of erlotinib in this setting. Here we report the case of a male Italian smoker with an adeno-carcinoma of the lung whose lung cancer and brain metastases have both responded to erlotinib.

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KRAS is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer.We divided NSCLC patients with mutation and RNA-seq data into KRAS mutated and wild type groups. Mann-Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a "transcriptomic fingerprint" of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using univariate and multivariate Cox regression analysis.Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3 and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p < 0.01). The KRAS signature also remained significant (p < 0.01) in a multivariate analysis including age, gender, smoking history and tumor stage.We generated a "surrogate signature" of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself.Despite advances in the last decade, lung cancer remains the most lethal tumor in women and men still exceeding the combined mortality of breast, prostate, colorectal and pancreatic cancers.1 Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer cases and is further classified into different subtypes including adenocarcinoma (AC), squamous cell carcinoma and large cell carcinoma.

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