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. 2022 Dec 6;14(23):6013.
doi: 10.3390/cancers14236013.

Clinical Potential of Circulating Cell-Free DNA (cfDNA) for Longitudinally Monitoring Clinical Outcomes in the First-Line Setting of Non-Small-Cell Lung Cancer (NSCLC): A Real-World Prospective Study

Valerio Gristina  1 , Nadia Barraco  1 , Maria La Mantia  1 , Luisa Castellana  1 , Lavinia Insalaco  1 , Marco Bono  1 , Alessandro Perez  1 , Delia Sardo  1 , Sara Inguglia  1 , Federica Iacono  1 , Sofia Cutaia  1 , Tancredi Didier Bazan Russo  1 , Edoardo Francini  2 , Lorena Incorvaia  1 , Giuseppe Badalamenti  1 , Antonio Russo  1 , Antonio Galvano  1 , Viviana Bazan  3
Affiliations

Clinical Potential of Circulating Cell-Free DNA (cfDNA) for Longitudinally Monitoring Clinical Outcomes in the First-Line Setting of Non-Small-Cell Lung Cancer (NSCLC): A Real-World Prospective Study

Valerio Gristina et al. Cancers (Basel). .

Abstract

Background: Despite the increasing implementation of targeted and immunotherapy-based treatments, the prognosis of patients with advanced NSCLC remains dismal. We prospectively evaluated longitudinal plasma cfDNA kinetics as an early marker of therapeutic efficacy in patients with advanced NSCLC undergoing standard first-line treatments.

Methods: From February 2020 to May 2022, treatment-naïve patients with advanced NSCLC were consecutively enrolled at the Medical Oncology Unit of the Paolo Giaccone University Hospital, Palermo (Italy). We quantified cfDNA in terms of ng/μL using a QubitTM dsDNA HS Assay Kit. The agreement between the cfDNA and radiologic response was evaluated from baseline (T0) to the radiologic evaluation (T1).

Results: A total of 315 liquid biopsy samples were collected from 63 patients at baseline, with a total of 235 paired plasma samples from 47 patients at disease re-evaluation. A fair concordance was observed between early and durable radiographic and cfDNA response (Cohen's kappa coefficient = 0.001); 11 and 18 patients receiving TKI (Pearson's chi-squared test = 4.278; Cohen's kappa coefficient = 0.039) and IO treatments (Pearson's chi-squared test = 7.481; Cohen's kappa coefficient = 0.006) showed a significant and durable association between cfDNA dynamics and the first radiologic evaluation, whereas among the 18 patients undergoing CT, no significant correlation was observed (Pearson's chi-squared test = 0.720; Cohen's kappa coefficient = 0.396). The ECOG-PS 2 patients presented with the mean baseline cfDNA levels 2.6-fold higher than those with ECOG-PS 0-1 (1.71 vs. 0.65 ng/µL; p = 0.105).

Conclusions: Our real-world study demonstrates that quantitative changes in cfDNA values correlated with responses to therapy and relapse of disease in treatment-naïve patients with advanced NSCLC undergoing TKI- and IO-based treatments.

Keywords: ECOG-PS 2; NSCLC; cfDNA; liquid biopsy; treatment monitoring.

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Conflict of interest statement

A.R. reported personal fees from Bristol, Pfizer, Bayer, Kyowa Kirin, Ambrosetti for advisory board activity and a speaker honorarium from Roche Diagnostics, outside from the submitted work. The remaining authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Graphical representation of cfDNA dynamics from baseline (T0) to the radiologic evaluation (T1).
Figure 2
Figure 2
Box-and-whisker plots showing the baseline and post-treatment cfDNA levels between the responders and non-responders. Note: cfDNA, cell-free DNA; *, outliers.
Figure 3
Figure 3
Kaplan–Meier analysis of the PFS and OS according to the cfDNA increase at first restaging in the overall cohort population. Note: cfDNA, cell-free DNA; PFS, progression-free survival; OS, overall survival.
See this image and copyright information in PMC

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