Abstract 59P
Background
Recent technological advances now allow the detection of minute amounts of cell-free tumor-derived DNA (ctDNA) in blood plasma. Therefore, ctDNA analyses can facilitate the diagnosis, monitoring, and tracking of minimal residual disease (MRD) of cancer patients. Given the clinical need of a sensitive and specific biomarker for monitoring of paediatric and adolescent sarcoma patients, we implemented a longitudinal ctDNA monitoring workflow for paediatric sarcoma patients into clinical routine.The aim of the observational study was to analyze if changing levels of ctDNA are associated with treatment response and long-term outcome.
Methods
Since the detection of fusion breakpoints is one of the most sensitive detection method for ctDNA, we designed patient-specific ddPCR assays to track ctDNA in blood plasma collected before, during, and after therapy. To this end, fusion breakpoints were established from whole genome sequencing data of tissue samples. Overall, 19 children and young adults (10 female, 9 males) with a mean of 12 years (range 2-19) were analyzed. Of those, 15 had Ewing sarcomas (ES) and 4 other fusion-related sarcomas.
Results
ctDNA levels assessed as copies of fusion breakpoints were clearly associated with treatment response. In patients with durable response ctDNA declined and remained low or undetectable. In contrast, in patients with unfavorable clinical courses, ctDNA dynamics were more volatile and rising ctDNA level indicated recurrence and progression. Although changing ctDNA levels correlated well with clinical outcome within individual patients, a high variability was observed between patients. Moreover, ctDNA levels did not correlate with tumor burden or other risk factors.
Conclusions
Our data prove practical feasibility for real-time ctDNA monitoring in sarcoma patients. Once the breakpoint and the respective assays are established, ddPCR can be performed within one day and provide useful data of molecular responses. The evidence of increasing amounts of ctDNA or its absence clearly helps in the treatment decision making process (e.g. as indicator of suspected recurrence or treatment response, respectively).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Medical University of Graz.
Funding
Has not received any funding.
Disclosure
A. Leithner: Financial Interests, Institutional, Other, Institutional educational grant: Johnson & Johnson, Alphamed, Medacta, Implantec; Non-Financial Interests, Personal, Other, Board Member: European Musculoskeletal Society (EMSOS); Non-Financial Interests, Personal, Other, Board member: International Society of Limb Salvage (ISOLS); Non-Financial Interests, Personal, Leadership Role: Austrian Society of Orthopaedic Surgeons (ÖGO); Non-Financial Interests, Personal, Member: Connective Tissue Oncology Society (CTOS). All other authors have declared no conflicts of interest.