EJ-1 - Translational Research in Lung Cancer: From the Perspective of the European Thoracic Oncology Platform(Etop)

Abstract

ETOP was founded in 2009 to promote research in lung cancer. The first translational project, Lungscape, was designed to address the challenges of studying the pathological and molecular characteristics of resected lung cancer in order to expedite the knowledge of current and evolving clinical and molecular biomarkers and their association with outcome in patients with early non-small cell lung cancer. Patient selection was based on radical surgical resection, overall availability of clinical annotations, at least 3 years of follow-up as well as adequate quantity and quality of formalin-fixed paraffin embedded tissue.In a first part surgical outcome was determined according to clinical and pathological criteria including 2449 cases from fifteen participating centers. The 5-year OS was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively. Lungscape is the first large series reporting on lung cancer surgical outcome including not only OS, but also RFS and TTR and including multivariate analysis of clinical and pathological prognostic parameters. The second project involved the prevalence and prognostic impact of ALK gene fusion. Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tissue sections of 1281 adenocarcinoma cases with available comprehensive clinical data Lungscape biobank. The prevalence of ALK+ was 6.4% using IHC and at least 2.2% using FISH. Multivariate models - adjusted for patient, tumor and treatment characteristics - and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better OS. Ongoing studies include MET, PI3K and multiplex mutation testing.From its initiation, the plan was to expand to a prospective biomarker study on patients with advanced non-small cell lung cancer and to provide tailored clinical trials. This is now being realized in collaboration between ETOP the EORTC in SPECTAlung and will include at its start over 10 European centers in different countries. The platform will be complemented by a master protocol which allowing access to clinical trials based on molecular tumor characteristics. SPETAlung will encompass not only non-small cell lung cancer, but also mesothelioma and thymic malignancies.