title: [Lung cancer screening in high-risk subjects: early detection with LDCT and risk stratification using miRNA-based blood test].
abstract: Lung cancer still remains a high mortality disease in the face of developments in diagnostic and therapeutic methods that occurred in the last 20 years. The analysis of the experiences from the first studies - in which chest X-ray (CXR) was adopted, associated or not with sputum cytology - has failed to show a reduction in lung cancer specific mortality. Subsequent screening studies that have introduced the use of low-dose computed tomography (LDCT) have revealed a large number of early-stage lung cancers, thus potentially curable; however, this has not allowed us to demonstrate a decrease in lung cancer-specific mortality. With the results of the American study National Lung ScreeningTrial (NLST), published in 2011, for the first time a lung cancer-specific mortality reduction by 20% thanks to the use of LDCT compared to RXT, was highlighted. However, a false discovery rate of 96.4% was also described with an overdiagnosis that can be up to 78.9% for bronchioalveolar lung cancer. Due to the high sensitivity of LDCT, able to identify a non-calcified pulmonary nodule in one subject on two, it becomes necessary to avail instruments to more accurately identify suspicious nodules. Until some time ago, the possible use of lung tumour markers was not viable in view of the poor organ specificity. The study and development was, then, pushed to organ- and tissue-specific markers such as microRNA (miRNA), noncoding RNA sequences involved in many processes and expression of oncogenic activity of the microenvironment. The use of biomarkers such as circulating miRNA implemented in LDCT screening has highlighted a reduction of 5 times for the rate of false positives, going from 19.4% to 3.7%, with a sensitivity of 87%, a specificity of 81%, and a negative predictive value of 99%. The need to appropriately use the available resources commensurate with the disease to treat will push more and more towards the implementation of LDCT biomarkers based screenings, stable and easily reproducible, as circulating miRNAs, obviating to problems such as false positives, unnecessary procedures of invasive surgery for benign lesions, and optimizing the cost benefit ratios.The development of new specific biomarkers appears to offer new promising prospects.
authors.affiliation: Struttura complessa di chirurgia toracica, Fondazione IRCCS Istituto nazionale dei tumori, Milano.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sestini
authors.affiliation: Struttura complessa di genomica tumorale, Dipartimento di oncologia sperimentale, Fondazione IRCCS Istituto nazionale dei tumori, Milano.
authors.forename: Mattia
authors.initials: M
authors.lastname: Boeri
authors.affiliation: Dipartimento di diagnostica per immagini e radioterapia, Fondazione IRCCS Istituto nazionale dei tumori, Milano.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Marchianò
authors.affiliation: Dipartimento di scienze cliniche, Unità operativa di radiologia, Università di Parma.
authors.forename: Mario
authors.initials: M
authors.lastname: Silva
authors.affiliation: Dipartimento di diagnostica per immagini e radioterapia, Fondazione IRCCS Istituto nazionale dei tumori, Milano.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Calareso
authors.affiliation: Dipartimento di statistica e metodi quantitativi, divisione di biostatistica, epidemiologia e salute pubblica, Unità di ricerca sanitaria e farmacoepidemiologia, Università degli Studi di Milano-Bicocca.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Galeone
authors.affiliation: Struttura complessa di genomica tumorale, Dipartimento di oncologia sperimentale, Fondazione IRCCS Istituto nazionale dei tumori, Milano.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.affiliation: Struttura complessa di chirurgia toracica, Fondazione IRCCS Istituto nazionale dei tumori, Milano. ugo.pastorino@istitutotumori.mi.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
mesh_terms: D055088:Early Detection of Cancer; D006403:Hematologic Tests; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000175:diagnosis*; D035683:MicroRNAs
chemical_list: D035683:MicroRNAs