New Insights from Long-Term Clinical Use of Circulating Tumor DNA-Based Minimal Residual Disease Monitoring in Translocation-Associated Sarcomas.

\n<bold><italic>Introduction:</italic></bold> Assessment of circulating tumor DNA (ctDNA) as a means to monitor disease activity in translocation-associated tumors has become very popular in clinical practice. However, there are still few studies on its clinical application to date. Our study evaluates the clinical applicability of ctDNA as a biomarker for monitoring minimal residual disease (MRD) in patients with translocation-associated sarcomas. <bold><italic>Methods:</italic></bold> In this retrospective study, we correlated 285 ctDNA samples from 34 patients diagnosed with translocation-associated sarcoma with the clinical course and images. Blood samples were collected at multiple time points during follow-up (median: 97 weeks, range: 7–398). <bold><italic>Results:</italic></bold> We discovered a significant association between ctDNA levels and the clinical course of the disease, particularly noting differences between patients in remission or with progressive disease (<italic>p</italic> = 0.001). Furthermore, although we noted that ctDNA levels remained undetectable in a few cases of unilocular recurrence (<italic>n</italic> = 3), they were consistently higher in patients with multilocular recurrence (<italic>n</italic> = 14; <italic>p</italic> = 0.008). <bold><italic>Conclusion:</italic></bold> Monitoring ctDNA levels provides highly specific, additional information enabling early recurrence detection in patients with translocation-associated sarcomas during the follow-up and can be integrated into clinical practice. However, MRD monitoring by ctDNA quantification alone does not allow the reliable detection of 100% of unilocular recurrences and should be complemented by the use of conventional imaging techniques. This study investigates the emerging use of circulating tumor DNA (ctDNA) as a method to monitor the tumor burden in patients with a specific group of cancers called translocation-associated sarcomas. These rare cancers result from particular genetic changes called translocations. ctDNA is genetic material shed into the blood by tumor cells. Thus, ctDNA (with the tumor-specific translocation) detected in the blood of patients may represent a surrogate parameter for the presence of active tumor cells, serving as a genetic tumor marker. We analyzed 285 blood samples from 34 patients with translocation-associated sarcomas taken at different time points in the patients’ follow-up period of 7–398 weeks (2 years on average) to see how ctDNA levels correlated with the course of their disease. Our study found that ctDNA levels were strongly linked to a treatment response or recurrence of the disease. In tumor-free patients, ctDNA levels were undetectable. However, where the disease returned – especially if these levels were detectable in multiple areas – ctDNA levels went up again. In summary, using ctDNA analyses in translocation-associated cancers is a valuable, rather sensitive, and highly specific additional tool for monitoring the treatment response and for early detection of a recurring disease. [ABSTRACT FROM AUTHOR]