(P 297) ANALYSIS OF CTDNA KINETICS IN PATIENTS WITH METASTATIC LEIOMYOSARCOMA UNDERGOING LOCOREGIONAL PROCEDURAL INTERVENTION

Objective: In patients affected with metastatic leiomyosarcoma (LMS), locoregional interventions are often undertaken to maximize disease control and palliate symptoms. Circulating tumor DNA (ctDNA) in the blood are a promising non-invasive modality to assess changes in disease burden in real time. Data are needed to guide interpretation of ctDNA kinetics peri-intervention to assess their correlation with patient outcomes.

Methods: This retrospective study includes patients with metastatic LMS who underwent locoregional procedures (surgery, radiation, ablation, or embolization) at Stanford Sarcoma Center between October 2020 and June 2025. Blood samples were collected as part of routine clinical care, and ctDNA analysis was performed using a clinically validated, personalized, tumor-informed mPCR-NGS assay (Signatera, Natera, Inc). Progression was identified by routine imaging (CT or MRI). Patients who had ctDNA assessed within 8 weeks prior to locoregional procedure and a second ctDNA level within 8 weeks after the procedure were included in the analysis. If the same patient had multiple procedures with serial ctDNA collection, the earliest procedure was included to maximize follow-up.

Results: Forty-seven patients with metastatic LMS were included in the analysis, median age at diagnosis 55 (range 29 – 74 years), 89% female, 62% uterine. Nearly half underwent surgical metastasectomy/debulking (53%); the remaining underwent radiation (30%), ablation (9%), or embolization (6%). Patients underwent baseline ctDNA collection at median of 26 days (range 0 – 56) prior to procedure and follow-up ctDNA collection at median 25 days after the procedure (range 2 – 55 days). At median follow-up of 14.1 months (range 0.5 – 50.7 months), median progression-free survival (PFS) for the entire cohort from date of procedure was 5.6 months (95% CI 4.4 – 10.2 months), and median overall survival (OS) from date of procedure was 50.7 months (95% CI 32.8 – not reached). Compared to patients who had decline or unchanged ctDNA level, patients who experienced any rise in ctDNA level (n = 15 or 32%) had worse PFS (ctDNA rise vs no rise: 3.6 months vs. 6.1 months, p = 0.03). Median OS was not statistically different between the two groups (ctDNA rise vs no rise: 50.7 months vs not reached, p = 0.3).

Conclusion: Our results suggest that rise in ctDNA in the blood within 8 weeks after locoregional intervention correlates with worse outcomes. Studies are underway to assess these findings in a prospective design.