Enhancing soft tissue sarcoma surveillance: The role of ctDNA testing in early detection and monitoring beyond traditional imaging.

Abstract

11577 Background: Soft tissue sarcoma (STS), particularly large (>5 cm), intermediate to high grade, and aggressive subtypes, is associated with high relapse rates, necessitating effective surveillance. Traditional methods, including physical exams and radiologic imaging, can be inconclusive, leading to radiation exposure. Circulating tumor DNA (ctDNA), a biomarker from tumor-derived cell-free DNA in the bloodstream, offers a potential solution for early recurrence detection and treatment monitoring. While ctDNA has shown promise in various cancers, its role in STS remains under-explored. Methods: We conducted a retrospective analysis of localized, high-risk STS patients who underwent surgery, followed by standard imaging, physical exams, and Signatera ctDNA testing from April 2023-January 2025. The study evaluated the concordance between ctDNA positivity and imaging findings, with a subgroup analysis exploring metastatic patterns and molecular profiles in ctDNA-positive patients. Mann-Whitney test was conducted to evaluate the difference in time to progression between ctDNA and imaging. Results: The cohort consisted of 63 STS patients, including 501 plasma samples for Signatera ctDNA testing alongside routine imaging. The patient population was 52% female, 35% Hispanic, and 80% White. ctDNA assay was performed on an average of 8 ± 4 plasma samples per patient, over a median surveillance duration of 12 months. Of the 63 patients, 18 tested positive for ctDNA. There was no significant difference (p=0.984) in the time to progression between ctDNA testing (35 ± 17.6 months) and radiological imaging (34.3 ± 18.5 months). Our data also revealed that all patients with negative ctDNA results had corresponding negative imaging findings. In the subgroup analysis of ctDNA-positive patients, majority had pulmonary metastasis (7, 39%), followed by liver metastasis (3, 16%). Molecular profiling demonstrated significant heterogeneity, with TP53 mutations being the most common alteration, present in 4 (22%) patients. Conclusions: Our study demonstrates the potential utility of ctDNA testing in monitoring high-risk STS patients. ctDNA showed no significant difference in time to progression compared to traditional imaging and offers a non-invasive alternative with strong concordance with imaging results, particularly for patients with negative ctDNA findings. These findings underscore the potential of ctDNA as a complementary tool to traditional surveillance methods, potentially reducing reliance on radiologic imaging and enhancing personalized treatment strategies. Most common STS subtypes and ctDNA positivity. STS subtypes Total number of patients Positive ctDNA testing (%) Leiomyosarcoma 15 5 (33.3) Synovial Sarcoma 7 2 (28) Liposarcoma 5 3 (60) Myxofibrosarcoma 4 0 (0) Fibroblastic 4 1(25) Pleomorphic 3 1(33.3) Angiosarcoma 3 1(33.3) Others 22 5(22)