Abstract
AIMS: We aimed to explore the prognostic role of circulating DNA-related markers to improve clinical decision-making in patients with lung malignancies. METHODS: A systematic search was performed on PubMed, Scopus, and Web of Science. RESULTS: 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. CONCLUSION: 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.