Prognostic and predictive factors in resected NSCLC

Lung cancer is the leading cause of cancer deaths in men and increasingly also in women in most industrialized countries. Non-small-cell lung cancer (NSCLC) comprises about 80% of all lung cancers. NSCLC stage I-IIIA is treated by surgery with curative intent. Despite complete tumor resection, however, many patients relapse. Randomized trials evaluating postoperative adjuvant chemotherapy gave inconclusive results but a meta-analysis of these trials suggests an absolute survival benefit of 5% at 5 years. Because of better antiemetics, more active chemotherapy protocols and the results of the meta-analysis, adjuvant chemotherapy is currently re-evaluated in large clinical trials. The largest of these trials is the International Adjuvant Lung Cancer Trial (IALT), a world- wide trial evaluating the impact of adjuvant cisplatin-based chemotherapy on survival in patients with completely resected stage I-IIIA NSCLC as compared to surgery alone. The present research project is a translational research part of IALT. The overall goal of the present project is to characterize molecular markers with prognostic or predictive significance in IALT patients. To achieve this, we will determine the relationship between the expression or mutations of several molecular markers in tumors and survival (disease-free survival, overall survival) of IALT patients. This relationship will be studied for the total study population, for patients receiving adjuvant chemotherapy and for those receiving no adjuvant chemotherapy. As molecular markers we have selected factors previously shown to be of prognostic or predictive value in NSCLC and/or factors that are involved in response or resistance to anticancer drugs. The expression of the following molecular markers will be studied by appropriate detection methods: LRP, MLH1, MSH2, p16/INK4A, p27/Kip1, HER-2/neu, and K-ras. The results of our research project should contribute to the understanding of the drug resistance in NSCLC and might lead to the development of new treatment strategies. The results might also have a major impact on the clinical management of patients with completely resected NSCLC in the future. Some of the molecular markers might be helpful for the selection of those patients who benefit from adjuvant chemotherapy after complete resection of their primary tumors.