Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials

SIMPLE SUMMARY: Cell-free DNA is present in the plasma and serum of healthy subjects, however, its level is usually much higher in people after physical effort, patients with various diseases such as trauma, sepsis, and also in patients with some cancers. In this concise review, we show the current state of cell-free DNA applications based on clinical trials registered until April 2021. Furthermore, we attempt to summarize a large number of clinical trials and resolve discrepancies raised by these trials. Despite a large number of trials, more studies should include at least 1000 participants and be conducted in large multicenter projects in order to find more accurate results before cfDNA can replace standard diagnostics or often ineffective and hazardous biopsy. ABSTRACT: We aimed to summarize the current knowledge about the trends in cfDNA application based on the analysis of clinical trials registered until April 2021. International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov were searched with the keywords: “cf-DNA”; “Circulating DNA”; “Deoxyribonucleic Acid”; and “Cell-Free Deoxyribonucleic Acid”. Of 605 clinical trials, we excluded 237 trials, and 368 remaining ones were subject to further analysis. The subject, number of participants, and study design were analyzed. Our scoping review revealed three main trends: oncology (n = 255), non-invasive prenatal diagnostic (n = 48), and organ transplantation (n = 41), and many (n = 22) less common such as sepsis, sport, or autoimmune diseases in 368 clinical trials. Clinical trials are translating theory into clinical care. However, the diagnostic value of cfDNA remains controversial, and diagnostic accuracy still needs to be evaluated. Thus, further studies are necessary until cfDNA turns into a standard in clinical practice.