The prognostic role of circulating DNA markers in patients with lung malignancies: a systematic review and meta-analysis

We aimed to explore the prognostic role of circulating DNA-related markers to improve clinical decision-making in patients with lung malignancies. A systematic search was performed on PubMed, Scopus, and Web of Science. About 133 articles were included, comprising 5750 EGFR-positive, 1583 ALK-positive, and 9657 patients without specified genetic groups. Circulating tumor DNA (ctDNA) response was a significant prognostic marker associated with improved overall survival (OS) (HR = 0.36 [0.27, 0.47], I2 = 0%) and progression-free survival (PFS) (HR = 0.31 [0.18, 0.55], I2 = 67.33%) in advanced non-small cell lung cancer (NSCLC). Meta-analysis of tumor mutational burden (TMB) in the same group demonstrated trends toward poorer survival outcomes for higher TMB -pooled HR of 1.63 (95%-CI: 0.92, 2.88, I2 = 71.23%) for OS and 1.09 (95%-CI: 0.63, 1.89, I2 = 86.66%) for PFS. Finally, meta-analysis in advanced EGFR-positive NSCLC implicated significant prognostic effect of EGFR response positivity on OS and PFS -pooled HR of 0.39 and 0.27, respectively. Circulating DNA markers entailed valuable information in patient prognostication and depicting treatment efficacies in lung cancer. Further studies are needed to decipher more robust criteria for the presently accepted markers – namely ctDNA and EGFR response measures. Additionally, there are several markers – i.e. TMB – that have more exploratory clinical benefits.