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. 2024 Mar:41:101869.
doi: 10.1016/j.tranon.2023.101869. Epub 2024 Jan 29.

Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression

Marzia Del Re  1 , Giovanna Irene Luculli  2 , Iacopo Petrini  3 , Andrea Sbrana  3 , Vieri Scotti  4 , Diego de Miguel Perez  5 , Lorenzo Livi  6 , Stefania Crucitta  2 , Mauro Iannopollo  7 , Francesca Mazzoni  8 , Martina Ruglioni  2 , Carmelo Tibaldi  9 , Emanuela Olmetto  4 , Irene Stasi  10 , Editta Baldini  9 , Giacomo Allegrini  10 , Lorenzo Antonuzzo  11 , Franco Morelli  12 , Andrea Pierini  13 , Nicola Panzeri  13 , Stefano Fogli  2 , Antonio Chella  3 , Christian Rolfo  5 , Romano Danesi  14
Affiliations

Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression

Marzia Del Re et al. Transl Oncol. 2024 Mar.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Liquid biopsy; NGS; NSCLC; Predictive biomarkers; Resistance to treatment.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig 1
Fig. 1
Concomitant alterations in NSCLC patients at diagnosis. (A) Actionable variants detected in NSCLC patients. (B) Non-actionable variants detected in NSCLC patients.
Fig 2
Fig. 2
ESCAT classification of driver alterations detected in NSCLC patients at diagnosis.
Fig 3
Fig. 3
Concomitant alterations in NSCLC patients at disease progression. (A) Actionable variants detected in NSCLC patients. (B) Non-actionable variants detected in NSCLC patients.
Fig 4
Fig. 4
ESCAT classification of alterations detected in NSCLC patients at disease progression.
Fig 5
Fig. 5
Representation of resistance mechanisms identified in patients at disease progression, depending on previously administered therapy and driver alterations.
See this image and copyright information in PMC

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