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Del Re, Marzia; Luculli, Giovanna Irene; Petrini, Iacopo; Sbrana, Andrea; Scotti, Vieri; Perez, Diego de Miguel; Livi, Lorenzo; Crucitta, Stefania; Iannopollo, Mauro; Mazzoni, Francesca; Ruglioni, Martina; Tibaldi, Carmelo; Olmetto, Emanuela; Stasi, Irene; Baldini, Editta; Allegrini, Giacomo; Antonuzzo, Lorenzo; Morelli, Franco; Pierini, Andrea; Panzeri, Nicola; Fogli, Stefano; Chella, Antonio; Rolfo, Christian; Danesi, Romano
Translational oncology, 03/2024, Volume: 41Journal Article
•Utility of ctDNA analysis by Next Generation Sequencing in patients with NSCLC.•Driver druggable variants were detected in patients at diagnosis and at progression.•Liquid biopsy allows detection of tumour heterogeneity in NSCLC patients. The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients. Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses. Gene variants were classified accordingly to the ESCAT score. A total of 106 patients were included in this study; 44 % of cases were requested because of tissue unavailability at the diagnosis and 56 % were requested at the PD. At least one driver alteration was observed in 62 % of cases at diagnosis. Driver druggable variants classified as ESCAT level I were detected in 34 % of patients, including ALK-EML4, ROS1-CD74, EGFR, BRAF, KRAS p.G12C, PI3KCA. In the PD group, most patients were EGFR-positive, progressing to a first line-therapy. Sixty-three percent of patients had at least one driver alteration detected in blood and 17 % of patients had a known biological mechanism of resistance allowing further therapeutic decisions. The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA.
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