Role of circulating tumor DNA in metastatic appendiceal neoplasms: A systematic review

Background: Circulating tumor DNA (ctDNA), tumor DNA fragments detected in blood sourced from primary malignancy, is an emerging non-invasive tool in oncology for screening, diagnosis, and surveillance. Here, we analyze its utility in patients with metastatic appendiceal neoplasms. Methods: Following PRISMA guidelines, PubMed, Cochrane, and Clinicaltrials.gov were searched for ‘Appendiceal Neoplasms’ AND ‘Circulating Tumor DNA’. Four original studies reporting the role of ctDNA in appendiceal cancer were included after screening 195 articles. Results: A total of 196 patients were included in the review. (Table) The total number of collected samples was 209 and 41% were tested positive for ctDNA. Singh et al. 2023 reported eight stage IV appendiceal cancer patients with the median age of 64.5 (45–75) years. 37.5% were tested positive for ctDNA while 37.5% had undetectable ctDNA despite having residual peritoneal disease and 25% had insufficient DNA from tumor specimen. López-Rojo et al. 2020 reported 50% ctDNA positive rate. All included patients had KRAS mutation and received hyperthermic intraperitoneal chemotherapy (HIPEC). On 36.5 months follow-up all the patients were alive but one out of two ctDNA positive patients had a relapse at 39 months followup. Kothary et al. 2022 reported 51% ctDNA positivity and 11% had longitudinal ctDNA measurements available which correlated well with their disease course. Zeineddine et al. 2023 collected 160 blood samples from 147 patients. Of 75% with radiographically metastatic disease, 38% had positive ctDNA while out of 25% with no radiographically metastatic disease, 38% had positive ctDNA. The overall survival and progression free survival for ctDNA positive patients was 46.2 months and 60 months, respectively, versus not reached for ctDNA negative patients. When stratified according to tumor grade, the ctDNA detection rate was 22% for well-differentiated, 39% for moderately differentiated, and 49% for poorly differentiated tumors. Conclusions: The use of ctDNA in metastatic appendiceal tumor is not widespread and detection rates are heterogenous. It was observed more in poorly differentiated appendiceal cancers but further studies are needed to evaluate its utility in clinical practice. Research Sponsor: None.