Abstract
Circulating tumor DNA (ctDNA) provides a minimally invasive tool for assessing tumor burden and genetic evolution in diffuse large B-cell lymphoma (DLBCL). This systematic review and meta-analysis evaluated 53 studies reporting the association of ctDNA and survival outcomes. High ctDNA concentration at baseline was associated with increased progression risk (hazard ratio (HR): 2.50, 95% confidence interval (CI) 2.15-2.9). The prognostic power of ctDNA intensified during treatment, with end of treatment (EOT) positivity showing the strongest association (HR: 13.69, 8.37-22.39). In patients with a negative EOT positron emission tomography (PET) scan, positive ctDNA was highly specific (90.8%) for subsequent relapse. Critically, in patients with a positive EOT PET scan, a negative ctDNA result decreased the risk of relapse (negative likelihood ratio 0.15, 0.06-0.3). ctDNA concentration reliably reflects tumor burden and treatment response, refining PET findings. Future studies should standardize ctDNA protocols and assess the feasibility of ctDNA-based DLBCL management.