The present study aimed to investigate the potential of basal cell-free fluorometric DNA
(cfDNA) quantification as a prognostic biomarker in advanced non-small cell lung cancer (NSCLC)
patients treated with an Immune Checkpoint Blockade (ICB). A discovery and validation cohort of 61
and 31 advanced lung cancer patients treated with ICB were included in this study. Quantification of
cfDNA concentration was performed before the start of the treatment and patients were followed up
for a median of 34 (30–40) months. The prognostic predicted value of cfDNA was evaluated based on
ROC, and Cox regression was conducted via univariate and multivariate analyses to estimate the
hazard ratio. We observed that a cfDNA cut-off of 0.55 ng/ L before the ICB determines the overall
survival of patients with a log rank p-value of 3.3 104. That represents median survivals of 3.8
vs. 17.5 months. Similar results were obtained in the validation cohort being the log rank p-value
3.8 102 with median survivals of 5.9 vs. 24.3. The univariate and multivariate analysis revealed
that the cut-off of 0.55 ng/ L before ICB treatment was an independent predictive factor and was
significantly associated with a better survival outcome. High cfDNA concentrations identify patients
with advanced NSCLC who do not benefit from the ICB. The determination of cfDNA is a simple test
that could select a group of patients in whom new therapeutic strategies are needed.