213 - Circulating Tumor DNA (ctDNA) as an Early Predictive Biomarker of Response In Locally Advanced Cervical Cancer Treated with the Interlace Regimen: A Preliminary Report

Purpose/Objective(s): The INTERLACE trial recently demonstrated that induction chemotherapy followed by chemoradiotherapy (CRT) improves outcomes for locally advanced cervical cancer. However, reliable biomarkers to stratify risk and personalize post-treatment surveillance in this context are lacking. This preliminary report investigates the utility of ctDNA as a non-invasive marker of treatment response and an early predictor of outcome.

Materials/Methods: Following IRB approval, we reviewed response to therapy in patients with locally advanced cervical cancer treated at our institution between Oct 2022 and January 2026. Serum ctDNA was measured using the Signatera™ test (Natera Inc.) at baseline (pre-chemotherapy), mid-CRT, end-of-CRT, and during follow-up (1, 3, 6 months, then every 6 months post-CRT). Correlations between ctDNA levels and imaging (PET-CT and MRI) were also assessed. Statistical analysis included paired T-tests for ctDNA changes over time and Chi-Square tests for correlation with radiographic response.

Results: Among a total of 213 serial ctDNA blood draws from 32 patients with locally advanced cervical cancer, 44 serial ctDNA blood draws were obtained from 8 patients treated with INTERLACE regimen. The median number of draws per patient was 6 (range, 2-9), with a median follow-up of 6 months (range, 1-12 months). Median patient age was 51 years (range, 27-73). All patients with measurable disease at baseline had detectable pre-chemotherapy ctDNA (median 2.52 MTM/ml; range, 0.18-27.98 MTM/ml). A significant reduction in ctDNA was observed from pre-chemotherapy to pre-radiotherapy (p=0.05), with 5 patients (62.5%) achieving undetectable ctDNA and 3 (37.5%) remaining detectable. While all patients achieved undetectable ctDNA by the end of CRT (p=0.0004), one patient with detectable ctDNA mid-CRT subsequently experienced radiographic recurrence 9 months later. All other patients with undetectable mid-CRT ctDNA remained disease-free during follow-up. A strong correlation was observed between elevated mid-CRT ctDNA and increased FDG uptake/measurable disease on imaging throughout treatment and follow-up (p = 0.005).

Conclusion: ctDNA is elevated in patients with locally advanced cervical cancer prior to starting the treatment as per INTERLACE. There was a reduction in ctDNA through the treatment. A mid-way detectable ctDNA may serve as an early predictive biomarker of response. To our knowledge, these early results suggest that there is a role of ctDNA in the management of patients with locally advanced cervical cancer treated as per INTERLACE and warrant a larger cohort assessment in a prospective study.