3584 - Appraisal of Utility of ctDNA in Patients with Vulvar Cancer Treated with Radiation: Early Report

G. Wernicke¹, M. M. Shalamov², B. Gui³, L. Ottensoser³, B. Parashar³, and L. Potters⁴; ¹Department of Radiation Medicine, Northwell Health Cancer Institute, Lake Success, NY, ²American Medical Program at Tel Aviv University, Tel Aviv, Israel, ³Northwell, Lake Success, NY, ⁴Northwell, New Hyde Park, NY

Purpose/Objective(s): Treatment failures with adjuvant radiation (RT) may not be identified for months after treatment and require invasive tests to confirm disease progression. This study assessed whether ctDNA is elevated in patients with vulvar cancer and whether it can be used as a non-invasive marker of response to RT. Materials/

Methods: After IRB approval, patients with advanced vulvar cancer treated with definitive RT at our institution 2022 - 2024 were assessed. ctDNA was obtained and measured using Signatera™ test (Natera Inc.) pre-, mid-way, pre-boost and at the end of RT and in follow up at 1, 3, 6 and every 6 months post-RT/, respectively. A detectable ctDNA was defined as any level above 0.00 mean tumor molecules (MTM)/ml, whereas 0.00MTM/ml was considered undetectable. During and after RT, ctDNA decline to 0.00MTM/ml was defined as complete metabolic response (cMR) but a reduction without achieving 0.00MTM/ml in ctDNA value was a partial metabolic response (pMR). Correlation between ctDNA levels and imaging (PET-CT, MRI, CT) was also assessed. Statistical analyses used were descriptive statistics, t-tests, and a Spearman correlation coefficient (?).
Results: At a median follow up of 8 months (range, 2-20 months), a total of 42 serial ctDNA blood draws were obtained. Median age was 63 (range, 40-90 years). Median radiation dose was 6600 cGy (range, 6400-7000 cGy). All patients with measurable disease on imaging and physical exam had median pre-RT ctDNA 1.63 MTM/ml (range, 1.20- 3.52 MTM/ml). There was a 100% reduction in all ctDNA values from pre-RT to mid-RT (mean 1.78 vs. 0.04, p=0.02): 88% cMR and 12% pMR. A total of 100% cMR in ctDNA occurred from mid-RT to post-RT. All patients had 100% reduction in all ctDNA values from preRT- to post-RT (mean 1.78 vs. 0, p=0.03). In patients who sustained complete response to RT, the mid-RT and end-RT ctDNA draws exhibited a cMR (ctDNA of 0.00MTM/ml), which was sustained in follow-up. In one patient with pMR at mid-RT (0.30MTM/ml), there was a rise of ctDNA at 9 mo post-RT (0.64MTM/ml) and progression of disease on PET-CT which led to a surgical excision. There was a strong correlation between elevated ctDNA and FDG uptake/measurable disease on imaging (PET/MRI) pre-treatment (?=0.87, p < 0.0045), as well as between a ctDNA decline and decrease of disease on imaging post-RT/CRT (?=1, p < 0.0001).
Conclusion: There was a reduction in ctDNA from pre- to mid- to post- RT. A mid-RT ctDNA identified responders to RT; hence, this finding may serve as an early predictive biomarker of response. Elevated ctDNA correlated with measurable disease on imaging. These early promising results suggest the need to study ctDNA in a larger cohort, prospectively.