An update of Clinical value of circulating tumor DNA in esophageal cancer： a systematic review and meta- analysis

Abstract

Abstract Background Esophageal cancer is a deadly disease with limited therapeutic options. Circulating tumor DNA (ctDNA) could be a promising tool in this regard, although the data is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and list its current challenges. Methods We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), accord to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity. Results Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86–5.23) and PFS (HR = 4.28; 95% CI, 3.34–5.48) were worse in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01–1.28). In addition, the estimated MPR rate was 50% (95%CI:14%-86%) of patients changed positive to negative; and 51% (95%CI:33%-69%) for patients kept negative from beginning to end. We also found that TP53, NOTCH1, CCND1 and CNKN2A are most frequent mutation genes. Conclusions Detection of ctDNA had prognostic value for EC patients. Positive ctDNA is associated with poor prognosis. A standardized technique needs to be established in order to introduce ctDNA analysis into routine clinical practice. Longitudinal ctDNA monitoring might be a better strategy in the neoadjuvant therapy. In an era of personalized medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in esophageal cancer.