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Non-small cell lung cancer (NSCLC) is one of the deadliest diseases worldwide. Tissue biopsy is the current gold standard for the diagnosis and molecular profiling of NSCLC. However, this approach presents some limitations due to inadequate tissue sampling, and intra- and intertumour heterogenicity. Liquid biopsy is a noninvasive method to determine cancer-related biomarkers in peripheral blood, and can be repeated at multiple timepoints. One of the most studied approaches to liquid biopsies is represented by circulating tumour cells (CTCs). Several studies have evaluated the prognostic and predictive role of CTCs in advanced NSCLC. Despite the limitations of these studies, the results of the majority of studies seem to be concordant regarding the correlation between high CTC count and poor prognosis in patients with NSCLC. Similarly, the decrease of CTC count during treatment may represent an important predictive marker of sensitivity to therapy in advanced NSCLC. Furthermore, molecular characterization of CTCs can be used to provide information on tumour biology, and on the mechanisms involved in resistance to targeted treatment. This review will discuss the current status of the clinical utility of CTCs in patients with advanced NSCLC, highlighting their potential application to prognosis and to treatment decision making. [ABSTRACT FROM AUTHOR]

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients. [ABSTRACT FROM AUTHOR]

Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Recent advances in the understanding of the biology of tumors and in highly sensitive detection technologies for molecular analysis offer targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. However, our understanding of an individual patient's lung cancer is often limited by tumor accessibility because of the high risk and invasive nature of current tissue biopsy procedures. "Liquid biopsy", the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), offers a new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to more personalized treatment. In this review, we examined the clinical significance and uniqueness of CTCs and ctDNA from NSCLC patients, isolation and detection methods developed to analyze each type of circulating biomarker, and examples of clinical studies of potential applications for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to therapy. We also discuss challenges that remain to be addressed before such tools are implemented for routine use in clinical settings. [ABSTRACT FROM AUTHOR]

The treatment of advanced non-small cell lung cancer (NSCLC) has been revolutionized by immune checkpoint inhibitors (ICIs). The identification of prognostic and predictive factors in ICIs-treated patients is presently challenging. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) were evaluated in 89 previously treated NSCLC patients receiving nivolumab. Blood samples were collected before therapy and at the first and second radiological response assessments. CTCs were isolated by a filtration-based method. cfDNA was extracted from plasma and estimated by quantitative PCR. Patients with baseline CTC number and cfDNA below their median values (2 and 836.5 ng from 3 mL of blood and plasma, respectively) survived significantly longer than those with higher values (p = 0.05 and p = 0.04, respectively). The two biomarkers were then used separately and jointly as time-dependent covariates in a regression model confirming their prognostic role. Additionally, a four-fold risk of death for the subgroup presenting both circulating biomarkers above the median values was observed (p < 0.001). No significant differences were found between circulating biomarkers and best response. However, progressing patients with concomitant lower CTCs and cfDNA performed clinically well (p = 0.007), suggesting that jointed CTCs and cfDNA might help discriminate a low-risk population which might benefit from continuing ICIs beyond progression. [ABSTRACT FROM AUTHOR]

The treatment of advanced non-small cell lung cancer (NSCLC) has been revolutionized by immune checkpoint inhibitors (ICIs). The identification of prognostic and predictive factors in ICIs-treated patients is presently challenging. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) were evaluated in 89 previously treated NSCLC patients receiving nivolumab. Blood samples were collected before therapy and at the first and second radiological response assessments. CTCs were isolated by a filtration-based method. cfDNA was extracted from plasma and estimated by quantitative PCR. Patients with baseline CTC number and cfDNA below their median values (2 and 836.5 ng from 3 mL of blood and plasma, respectively) survived significantly longer than those with higher values (p = 0.05 and p = 0.04, respectively). The two biomarkers were then used separately and jointly as time-dependent covariates in a regression model confirming their prognostic role. Additionally, a four-fold risk of death for the subgroup presenting both circulating biomarkers above the median values was observed (p < 0.001). No significant differences were found between circulating biomarkers and best response. However, progressing patients with concomitant lower CTCs and cfDNA performed clinically well (p = 0.007), suggesting that jointed CTCs and cfDNA might help discriminate a low-risk population which might benefit from continuing ICIs beyond progression. [ABSTRACT FROM AUTHOR]