211 - The Prognostic Role of Circulating Tumor DNA In Vulvovaginal Cancers Undergoing Radiotherapy

Purpose/Objective(s): Radiation (RT)/chemo-radiation (CRT) management of vulvovaginal cancers is fraught with severe toxicity. Treatment failures may not be identified for months after treatment and require invasive tests to confirm disease progression. This study is aimed at assessing whether detectable ctDNA could be used as a non-invasive marker of response to RT/CRT for vulvovaginal cancers.

Materials/Methods: Following IRB approval, we reviewed response to therapy in patients with vulvovaginal cancer treated with RT/CRT at our institution between June 2022 and December 2025. Serum ctDNA was obtained and measured using Signatera™ test (Natera Inc.) pre-, mid-way, at the end of RT/CRT and in follow up at 1, 3, 6 and every 6 months post-RT/CRT, respectively. A detectable value of ctDNA was defined as any level above 0.00 mean tumor molecules (MTM)/ml, whereas 0.00MTM/ml was undetectable. Statistical analyses used were descriptive statistics, t-tests, and a Spearman correlation coefficient (?).

Results: A total of 120 serial ctDNA blood draws were obtained from 15 consecutive patients, with 10 Stage III diseases (67%), 4 stage II diseases (27%) and 1 stage IV disease (6%). Ten patients had vulvar squamous carcinoma, 3 had vaginal squamous carcinoma and 2 had vaginal melanoma. RT dose ranged from 5040cGy to 6400cGy for adjuvant cases, from 6400cGy to 7000cGy definitive case and from 3000cGy to 3600cGy in 5 fractions for melanoma. Median follow up was 19 months (range, 1-42 months). Median age was 70 (range, 37-91 years). A positive correlation was observed between elevated ctDNA and SUV/measurable disease on imaging pre-treatment (?=0.62, p = 0.003), as well as undetectable ctDNA and decline of SUV/complete resolution of SUV at 3-6 months following RT (p<0.0001). All 4 patients with radiographical progression/recurrence had detectable ctDNA levels which preceded imaging with median lead time of 122 days (range 6-184 days). One patient with undetectable ctDNA and negative imaging finding had symptom prompted biopsy proven subcentimeter urethral recurrence but negative on final surgery.

Conclusion: ctDNA is elevated in patients with vulvovaginal cancer. ctDNA dynamics correlated with imaging. Detectable ctDNA precedes radiographic evidence to detect progression/recurrence. These early promising results suggest that there is a role ctDNA in the management of patients with vulvovaginal cancer and warrant a larger cohort assessment in a prospective study.