BackgroundBrain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients.MethodsWe reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed.ResultsMedian Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038).ConclusionsPatients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment.

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Lung cancer is the major cause of cancer-related deaths and has a poor prognosis with a 5-yr overall survival of <10%, mostly due to lack of early stage diagnosis. Cigarette smoking is estimated to be responsible for >80% of the cases. Previous studies have demonstrated that former smokers have a higher risk of lung cancer compared to nonsmokers. Early detection of lung cancer would improve the overall survival of this disease. However, there is no validated screening test for lung cancer. To develop an early detection test, we selected saliva as the biofluid of choice due to its accessibility, protein content that provides diagnostic information on a variety of diseases, including cancer. To identify differentially expressed proteins in saliva from individuals with lung adenocarcinoma, whole saliva samples were collected from 6 patients with lung adenocarcinoma and 6 matched healthy controls (male individuals, >40 years, smokers >10 pack year). Proteins and peptides from whole saliva samples were analyzed by two-dimensional gel electrophoresis identifying 20 differentially expressed protein spots. Mass spectrometry analysis identified 63 peptides and revealed fourteen non-redundant proteins in saliva obtained from lung adenocarcinoma patients. Four of these proteins have been previously reported as serum biomarkers of cancer, and two of them were associated with non-small cell lung cancer. These potential biomarkers are being tested in an independent and larger cohort for validation. Patient-based saliva proteomics is a promising approach to searching for cancer biomarkers. Further characterization of these markers may provide the basis for new, noninvasive tests for screening, detection, and monitoring of high-risk individuals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4786. doi:1538-7445.AM2012-4786

e18028 Background: Brain metastases (BM) occur in 30-50% of non-small cell lung cancer (NSCLC) patients and confer worse prognosis and quality of life. Better selection of in-risk patients through an accurate biomarker could improve the benefit of prophylactic therapies. The aim of this prospective study was to determine a gene-expression profile (GEP) of primary tumor (PT) associated with BM in patients with advanced NSCLC. Methods: From January 2009 to June 2011, patients with stage IV of NSCLC were evaluated. PT core biopsy was performed prior to any treatment and snap-frozen. Samples with tumor cellularity > 70% and RNA integrity number > 8 were chosen for RNA isolation. A cDNA microarray platform representing 33,297 genes was used to obtain GEPs. All patients received standard chemotherapy. BM were confirmed by magnetic resonance imaging. Non- and supervised hierarchical clustering methods were employed to identify GEPs. Results: A total of 29 patients were enrolled, 79.4% (23/29) were adenocarcinomas, and 20.6% have other histology. BM were present in 15 (51.7%) patients, 14 at diagnosis and 1 was developed at 5 months of follow-up. Clinical characteristics were similar for patients with and without BM. At non- and supervised analyses, 35 genes up and down regulated were evidenced in BM group. From these, 11 transcripts with proteomic functions previously associated with metastasis processes were identified. Conclusions: Our work provides valuable biological information for development of predictive biomarkers for metastatic brain tumors from primary NSCLC. External validation of our gene-expression signature in a different set of patients is warranted. [Table: see text]