Circulating tumor DNA monitoring for early detection of disease recurrence in bone/soft tissue sarcoma.

11540 Background: Circulating tumor DNA (ctDNA) is a powerful, minimally invasive biomarker of treatment response and patient prognosis in many tumors. Here, we assessed the clinical performance of the Signatera assay in patients with bone and soft tissue sarcomas in assessing molecular residual disease (MRD). Methods: We performed a retrospective analysis of patients at our institution who underwent commercial ctDNA testing using the Signatera mPCR-NGS assays after curative intent resection of their primary tumor. Patients with oligometastatic disease were included if they also underwent resection of oligometastatic sites and did not have any evidence of residual disease. Additional inclusion criteria included three or more ctDNA draws in the MRD setting with at least one ctDNA blood collection within one of year of completing curative intent procedures and at least 6 months of clinical follow up after surgery. ctDNA positivity was defined as any detectable level of ctDNA at any time point in the patient’s treatment course after surgery. Results: We reviewed 305 patients who underwent Signatera ctDNA collection; 107 patients met the inclusion criteria for this study. The most common reason for not meeting inclusion criteria was advanced/unresectable disease (n = 168). The included 107 patients underwent over 1300 plasma ctDNA assessments in the MRD setting (average 12 ctDNA assessments per patient) between September 2019 and November 2025. For the overall cohort, sensitivity was 75% (36/48); specificity was 100% (36/36). One patient with angiosarcoma had ctDNA detected one month prior to data cut-off and was awaiting re-staging imaging. The largest represented histologies were leiomyosarcoma (n = 42) and undifferentiated pleomorphic sarcoma and related tumors (n = 22); sensitivity were 85% (22/26) and 57% (4/7), respectively. The median duration of follow-up after surgery was 41 months (range 1.6 to 79 months). Of the 48 patients with disease recurrence, 27 (60%) developed local disease recurrence only, 17 (38%) developed distant recurrence only, and 4 (9%) developed local and distant disease recurrence. The most common site of distant disease recurrence was in the lungs (n = 16). Sensitivity was lowest in the patients who developed disease recurrence isolated to the lungs (42%, 5 out of 12) compared to patients who developed disease recurrence not confined to the lungs (89%, 32 out of 36). Of the patients who had ctDNA detected at time of recurrence, 47% (17/36) demonstrated ctDNA positivity before detection of recurrence on imaging with an average lead time of 20 days. Conclusions: In a cohort of over 100 sarcoma patients with over 1300 plasma samples collected in the MRD setting, Signatera ctDNA assay demonstrated a clinical sensitivity of 75% and specificity of 100% for relapse detection with the highest sensitivity in leiomyosarcoma (85%) and when disease recurrence was not confined to the lungs (89%).