(P 01) FEASIBILITY OF A QUANTITATIVE METHYLATION-BASED CTDNA ASSAY IN PATIENTS WITH ADVANCED SARCOMAS

Objective: Circulating tumor DNA (ctDNA) is an emerging biomarker for monitoring treatment response, but its use across multiple cancer types, particularly in sarcoma, remains challenging. Northstar Response (NSR®) is a tissue-free, mutation-agnostic, pan-cancer therapy response monitoring assay that measures >500 cancer-specific methylated loci and precisely quantifies these loci with single-base-pair resolution. Quantification of these loci yields a tumor methylation score (TMS), which can be utilized as a surrogate of tumor burden. We evaluated the feasibility of using NSR in a real-world cohort of patients with advanced sarcomas to assess the detectability of ctDNA.

Methods: We performed a retrospective analysis of patients with advanced sarcomas who underwent NSR testing as part of routine care. All patients had at least one NSR test. For patients with serial testing, we performed correlations to radiographic or clinical response. Tumor methylation score (TMS) was expressed as Log10 values to normalize the skewed distribution.

Results: A total of 31 patients were analyzed. Among these patients, 19 (61%) had at least three ctDNA assays, and all had radiographic or clinical response assessments. The median age was 52 years (range, 19–82), with 54% of the participants being female. The breakdown of diagnoses was as follows: GIST (n = 6), SFT (n = 4), leiomyosarcoma (n = 4), and Other (n = 10). Baseline TMS-log10 showed statistically significant variation (p = 0.047) between these groups and was measurable in 28 patients (90%), with LMS having the highest ctDNA levels. Of the three patients with undetectable initial TMS, two developed detectable levels during their disease. Patients with progressive disease on their third assessment had rising TMS values more frequently, whereas decreases were more common in those with stable or responsive disease; however, this difference was not statistically significant (p = 0.35).

Conclusion: NSR testing was feasible in patients with advanced sarcoma and showed histology-specific variation. These findings support the potential of methylation-based circulating ctDNA for disease monitoring in sarcoma. Additional analyses of ctDNA dynamics and clinical outcomes are underway and will be presented.