Identification and monitoring of somatic mutations in circulating cell-free tumor DNA in lung cancer patients

Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

“…All this can be achieved by the introduction of this minimally invasive procedure that can be repeated several times throughout the disease progression without arm for the patients. Moreover, liquid biopsies provide a broader genetic characterization of the tumor reflecting its heterogeneity [9,36,40,49] and possibly identify disseminating aggressive clones.…”

“…Importantly, these (epi)genetic alterations seem to be highly concordant in blood ctDNA and in corresponding tumor tissues in a variety of cancers, including lung [17,29,42], breast [35], colorectal [17,44,50,52], pancreatic [32], liver [57], esophageal [17], gastric [6,43], and ovarian [17] cancers. In this sense, these minimallyinvasive and less risky liquid biopsies [57] could be used as an alternative to tissue biopsies in cases in which the latter cannot be performed [24,39,49] or when these do not gather enough high-quality DNA [17,39]. In fact, since 2016, non-small cell lung cancer (NSCLC) patients who are unable to provide tumor specimens can be tested for EGFR mutations in plasma, using the U.S. Food and Drug Administration (FDA)-approved cobas EGFR Mutation Test v2 [80].…”

“…For instance, ctDNA analysis has been successfully used to detect resistant mutations in genes such as EGFR [29,47], ERBB2 [43], PIK3CA, and RAS [28,50], in various cancers including NSCLC [28,29,47], CRC [50], and gastric cancer [43]. Moreover, monitoring the dynamics of ctDNA alterations is useful to predict response to treatment and clinical outcome [3,6,29,37,39,41,42,45,46,49], and allows to reorient treatment regimens in a more timely manner [25,59]. As a matter of fact, a ctDNA decrease after treatment has been associated with lower risk of progression [3,41,42] and longer survival [42], while persistent or increased ctDNA levels have been associated with progression [3,28,37,42,45,49,55], relapse [33,35,37], and decreased survival [35].…”

“…Moreover, monitoring the dynamics of ctDNA alterations is useful to predict response to treatment and clinical outcome [3,6,29,37,39,41,42,45,46,49], and allows to reorient treatment regimens in a more timely manner [25,59]. As a matter of fact, a ctDNA decrease after treatment has been associated with lower risk of progression [3,41,42] and longer survival [42], while persistent or increased ctDNA levels have been associated with progression [3,28,37,42,45,49,55], relapse [33,35,37], and decreased survival [35]. In particular, a promising study has shown that it might be possible to quantitatively predict the time needed for disease progression by combining longitudinal profiling of cfDNA and mathematical modeling [44].…”

Next Generation Sequencing-Based Profiling of Cell Free DNA in Patients with Advanced Non-Small Cell Lung Cancer: Advantages and Pitfalls

“…Again, the use of a 70-gene NGS panel allowed the identification of multiple and novel resistance alterations, evidencing a significant heterogeneity of gene mutations and of variant types both before and after the acquisition of resistance [78]. In a more recent report comparing ctDNA analysis using conventional methods (Real-Time PCR and ddPCR) and targeted NGS, the successful ability of a 11-gene NGS panel to identify therapeutic targets and monitor drug resistance in two independent cohorts of aNSCLC patients has been demonstrated, with turnaround times of only four days and a workflow for data interpretation easily implementable in clinical routine procedures [79].…”