Lung cancer is an aggressive disease with a high fatality rate; early diagnosis through screening is therefore paramount. Current strategies relying on Low-Dose Computed Tomography (LDCT), still show certain false positives rates, thus effective and validated methods to assist LDCT for early detection and to increase treatment efficacy are strongly needed to reduce mortality. Recently, non-invasive approaches based on biomarkers were proposed as promising for early detection and for informing on acquired cancer mutations involved in resistance to chemotherapy. In addition circulating tumor cells seem promising tool also to identify molecular alterations in oncogene addicted advanced nsclc patinets. Translation into preventive and clinical care is yet unfulfilled due to insufficient validation.
CLEARLY will focus on validation of a multifactorial "bio-radiomic" protocol for early diagnosis of lung cancer that combines circulating biomarkers and radiomic analysis. We will (a) assess the role of molecular and cellular biomarkers (exosomes, protein signatures, CTCs, microRNA) and radiomic signature, as complementary to assist early detection of lung cancer by LDCT, using bioinformatics techniques; (b) assess the prognostic role of CTCs including the role of cells epithelial mesenchymal transition (EMT) and (c) standardize a method for genomic analysis of CTCs for early detection of treatment resistance.
In a 2 years prospective study we have enrolled 150 lung tumor patients from Italy and Poland, 120 matched high-risk controls and additional 20 stage IV patients, collect biological samples and LDCTs, and evaluated biomarkers in blood and radiomic features in LDCTs. The sample size was calculated to allow a statistical power sufficient to identify predictive biomarker signatures with a p-value < 0.05.
Clinical endpoints: we assessed the molecular of circulating markers for early detection of lung cancer. The microrna seemed a promising diagnostic marker in early nsclc patients tool, metabolomic and proteomic signature have been analysed with initial interesting results to create increase accuracy of lung cancer screening. Radiomic tool to facilitate large-scale implementation needs additional clinical validation. Molecular analysis of circulating tumor cells in advanced oncogene addicted NSCLC improve showed the detection of molecular alteration in 100% of patients in a small group pf patinets who receied target therapy. Translational endpoints are: the circulating biomarkers are usefull tool to improve accuracy and specificity of lung cancer screening. A new liquid biopsy using CTC method is under evaluation to optimize target treatment in lung cancer patients with stage IV disease.
We expect that after additional analysis and external validation the study will produce and a bio-radiomic protocol for lung cancer screening, will characterize the genetic features of CTCs and explore their theranostic potential. These results, achieved by a transnational team of internationally recognized high-profile scientists, will accelerate the undertaking of lung cancer screening programs in Europe. The proposed biomarkers and methods could increase the ratio of screening positive cancer diagnosis, facilitate selection of screening candidates and help development of molecularly targeted drugs to stop lung cancer progression.