Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Advanced cancers, including non-small-cell lung cancer (NSCLC), have seen treatment advancements with tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs), and immune checkpoint inhibitors (ICIs).
• Plasma cell-free DNA (cfDNA) is emerging as a potential biomarker in oncology.

Purpose of the Study:

• To assess the prognostic value and efficacy prediction of plasma cfDNA in NSCLC patients undergoing chemotherapy, with or without precision therapies.
• To correlate cfDNA levels and kinetics with tumor burden, clinical features, survival outcomes, and treatment response.

Main Methods:

• Quantification of peripheral cfDNA levels in 154 NSCLC patients before and after the first chemotherapy cycle.
• Analysis of correlations between cfDNA metrics (baseline, post-chemotherapy, cfDNA Ratio) and clinical parameters including tumor burden, progression-free survival (PFS), disease-free survival (DFS), and objective response ratio (ORR).
• Stratification of cfDNA Ratio analysis by therapy regimen and NSCLC subtype (lung adenocarcinoma [LUAD] vs. lung squamous-cell carcinoma [LUSC]).

Main Results:

• Baseline cfDNA levels correlated positively with tumor burden, whereas post-chemotherapy levels did not.
• cfDNA kinetics, specifically the cfDNA Ratio (post- to pre-treatment cfDNA), effectively differentiated between responsive (CR/PR) and non-responsive (PD/SD) patients.
• A low cfDNA Ratio was associated with prolonged PFS and improved ORR in LUAD patients.
• The cfDNA Ratio showed significant predictive value in patients receiving chemotherapy plus VEGFIs, warranting further validation in other regimens and for LUSC.

Conclusions:

• Plasma cfDNA kinetics serve as a valuable prognostic biomarker and efficacy predictor in NSCLC patients undergoing chemotherapy.
• cfDNA Ratio is a promising tool for monitoring treatment response and predicting outcomes, especially in LUAD.
• Further research with larger cohorts is needed to confirm the utility of cfDNA Ratio across diverse NSCLC subtypes and treatment regimens.