Pulmonary neoplasms are, at the moment, the principal cause of death from cancer both in men and women. Non small-cell lung cancer (NSCLC) accounts for 80 to 85% of all lung cancer diagnosis, and these patients show a dismal 5-year survival of less than 15%. The development of brain metastasis in this type of patients diminishes their life expectancy to less than one year with a median survival of less than three months. When it comes to considering non small-cell lung cancer, approximately 50% of patients with locally advanced disease will develop brain metastasis at some time during the course of their illness. Moreover, the central nervous system (CNS) constitutes the first site of recurrence in 15 to 40% of these patients, and the autopsy studies have demonstrated that an important proportion of the patients that deceased because of advanced NSCLC present synchronic brain metastasis. Multiple studies exist in which by using microarrays of cDNA are able to evaluate the diagnosis, treatment and prognosis of lung cancer, and so, by using this molecular biology technique, the knowledge of lung cancer oncogenesis and pathophysiology has increased. However, there are no studies that specifically evaluate the relationship that exists between a genetic profile of the neoplastic cells from the primary lung cancer tumor and the development of metastasis to the CNS, with the purpose of distinguishing a subgroup of patients that will benefit of prophylactic treatment (as prophylactic cranial radiation).

Problem: What is the association between a genetic profile (to be obtained in this study by microarrays) of the primary tumor cells and the development of CNS metastasis in patients with NSCLC?

Justification: Obtaining a genetic profile from the primary NSCLC tumor cells, by using microarrays, where we can predict the development of CNS metastasis, may distinguish a subgroup of patients that, as with small cell lung cancer, could benefit from profilactic cranial radiation with which their quality of life and prognosis most probably will increase.

Principal objective: To determine the association between a genetic profile from the primary tumor cells and the development of central nervous system metastasis in patients with non small-cell lung cancer.

Hypothesis: A genetic profile (to be determined) from the primary tumor cells are associated with the development of central nervous system metastasis in patients with non small-cell lung cancer.

Material and methods: A clinical, prospective, analytic, open, non randomized, prognostic and observational cohort with a calculated sample of 66 patients with non-small cell lung cancer who authorize a biopsy study and that go to their regular lung cancer visits to the INCan or INER(National Institute of Cancerology and Respiratory Diseases) in the period from February 1, 2008 to February 1, 2009. A tissue biopsy from the primary lung cancer tumor will be obtained, a sample will be sent for the anatomical pathology service and another to the INMEGEN (National Institute of Genomic Medicine). This last institute will be in charge of performing the microarrays and the computer-based analysis in order to obtain the different genetic profiles that will be statistically analyzed to obtain the CNS metastasis development risk profile. Patients will be followed-up by means of the external consult of lung neoplasms. The statistical analysis will be performed using tests like Student's t or Mann-Whitney's U, chi-square or Fisher's exact test. A multivariate analysis of logistic regression will be performed. Global survival time will be analyzed using Kaplan-Meier's technique and the comparison between groups will be performed with log-rank test. The adjustment for potential confusors will be performed using multivariate regression analysis. A SPSS service package will be used for the analysis of data.

For result representation, we will use tables and graphs and pertinent measures will be taken to disclose the study.