Correlation between circulating tumor DNA (ctDNA) and disease status in soft tissue sarcoma patients: A pilot study.

Abstract

e23559 Background: Circulating tumor DNA (ctDNA) is used to monitor minimal residual disease (MRD), treatment response, and recurrence in patients with solid tumors including lung, colorectal, and breast cancers. Its utility in soft tissue sarcomas remains unknown. This pilot study aimed to evaluate the feasibility of detecting ctDNA in soft tissue sarcomas and how ctDNA correlates with radiologic surveillance. Methods: Two fellowship-trained orthopaedic oncologists used a personalized assay to quantify ctDNA for biopsy proven soft tissue sarcomas at presentation (baseline) and multiple follow-up time intervals from 2022-2025. Physicians were blinded to the ctDNA results. High grade sarcomas were treated with wide surgical resection and radiation and low-grade sarcomas were treated with surgical resection only. Surveillance was conducted with magnetic resonance imaging (MRI) of the affected limb and chest computed tomography (CT) scans. Results: 9 patients were included in this study (mean age 52.7 years, tumor diameter 12.4 centimeters, follow-up 10.9 months). 7 patients (78%) had a baseline ctDNA >0; 2 patients with low and intermediate grade sarcomas had ctDNA=0. The highest ctDNA was in a patient with metastatic disease on imaging. There was a statistically significant, strong positive correlation between tumor diameter, measured on MRI at the time of presentation, and baseline ctDNA (r=0.77, p=0.009). Follow-up ctDNA decreased to 0 in all patients who underwent surgical resection. In all patients who maintained a ctDNA of 0, their surveillance MRI and CT chest showed no evidence of disease. Conclusions: This pilot study demonstrates the feasibility of using an assay to detect ctDNA in various soft tissue sarcoma subtypes. Tumor size on presentation was associated with higher levels of ctDNA. This study is not without limitations, including the small sample size. A future large-scale study is planned to further evaluate the utility of this assay in evaluating patients with soft tissue sarcomas. Patient pathology, ctDNA, and radiographic information. Patient Pathology Baseline ctDNA Largest Diameter MRI (cm) Baseline CT Chest Most Recent ctDNA Most Recent Imaging Results Patient Status 1 High grade myxoid liposarcoma 7.41 14.8 Clear N/A N/A Lost to follow-up 2 High grade myxofibrosarcoma 254.77 16.4 Clear 0 NED NED 3 High grade UPS 15.29 19.1 Clear 0 NED NED 4 High grade UPS 85.92 11.2 Clear N/A N/A Deceased 5 Intermediate grade myxofibrosarcoma 0 4 Benign nodules 0 NED NED 6 High grade small round cell sarcoma 3317.32 19.5 Metastases N/A N/A Deceased 7 High grade pleomorphic rhabdomyosarcoma 4.08 4.4 Clear N/A N/A Awaiting follow-up 8 Low grade fibromyxoid sarcoma 0 7.7 Benign nodules 0 NED NED 9 Low grade extraskeletal myxoid chondrosarcoma 0.92 14.3 Clear N/A N/A Post resection, awaiting follow-up NED, No evidence of disease; UPS, undifferentiated pleomorphic sarcoma; cm, centimeters.