106 - Early Assessment of Response Using ctDNA as a Non-Invasive Biomarker in Patients with Gynecologic Malignancies Undergoing Radiotherapy

G. Wernicke¹, B. Gui², M. M. Shalamov³, L. Ottensoser², B. Parashar², and L. Potters⁴; ¹Northwell Health, New York, NY, ²Northwell, Lake Success, NY, ³American Medical Program at Tel Aviv University, Tel Aviv, Israel, ⁴Northwell, New Hyde Park, NY

Purpose/Objective(s): Radiotherapy (RT) causes toxicity and outcomes of treatment may not be known for months post-therapy. Early identification of response with a ctDNA blood draw may provide a non-invasive way to predict response to treatment. In this study, we used ctDNA to assess response to RT in patients with GYN cancers as early as mid-way during treatment. Materials/

Methods: After IRB approval, patients with vulvar, cervical, and recurrent endometrial cancer were treated with RT at our institution between 2022-2024. ctDNA was obtained using Signatera™ test pre-RT, mid-way through RT, pre-boost with brachytherapy or SBRT, at the end and in follow-up at 1, 3, 6 and every 6 months -post RT, 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. During and after RT, ctDNA of 0.00MTM/ml was defined as complete metabolic response (cMR) but a reduction without achieving the value 0.00MTM/ml in ctDNA was deemed partial metabolic response (pMR). Correlation between ctDNA levels and imaging (PET-CT, MRI, CT) was also assessed. Statistical analyses used were descriptive statistics, t-test, Chi-square test and a spearman-rank correlation coefficient (?).
Results: A total of 105 serial ctDNA blood draws were obtained from 21 patients with 8 (38%) vulvar, 7 (33%) cervical, 2 (10%) neuroendocrine, and 3 (19%) recurrent endometrial cancers (reEMCa). Median age was 59 years (range, 35-90 years). Median number of ctDNA draws per patient was 6 (range, 1-9). Median radiation dose was 5900 cGy (range, 4500-7000 cGy), brachy boost of 28Gy/4fx T&O and SBRT 30Gy/5fx for 7 cervix cases, and SBRT boost 2750cGy/5fx for reEMCa. There was 100% reduction in ctDNA values (metabolic response) from pre-to post-RT (mean 2.04 vs. 0, p=0.03): 75% cMR and 25% pMR. In patients who sustained response to RT, mid- and end-RT ctDNA draw exhibited 0.00MT/ml (undetectable), which continued in follow-up. A strong correlation was observed between elevated ctDNA and SUV/measurable disease on imaging pre-treatment (?=0.64, p = 0.01), as well as undetectable ctDNA and decline of SUV/complete resolution of SUV at 3-6 months following RT (p=0.045).
Conclusion: ctDNA in patients with gynecological malignancies drawn at pre-, mid- and post-RT sustained metabolic response and correlated with response to treatment by imaging and clinical exams. Our early findings suggest that a mid-treatment ctDNA test identified responders to RT and thus may serve as an early predictive biomarker of response. A larger prospective evaluation is warranted.