1279 - WGS-Based Personalized ctDNA Assay for Molecular Residual Disease (MRD) Detection in Locally Advanced Cervical Cancer Treated with Definitive Chemoradiotherapy: Interim Results from a Prospective Multicenter Study (MONSTAR-SCREEN-3)
Presenter(s)
M. Nakamura1, H. Saji2, F. Ito3, T. Chiyoda4, H. Kurosu5, Y. Suzuki2, K. Tsuchida2, M. Nagamine3, S. I. Kageyama6, K. Harano3, H. Tanabe3, T. Hashimoto3, T. Fujisawa3, H. Bando3, E. Oki7, J. Jasper8, K. J. Taber8, T. Yoshino3, and H. Watari5; 1Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 2Kanagawa Cancer Center, Yokohama, Japan, 3National Cancer Center Hospital East, Kashiwa, Japan, 4Keio University School of Medicine, Tokyo, Japan, 5Hokkaido University Graduate School of Medicine and Faculty of Medicine, Sapporo, Japan, 6Division of Translational Informatics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan, 7Kyushu University Hospital, Fukuoka, Japan, 8Myriad Genetics, Inc., Salt Lake City, UT
Purpose/Objective(s):
After chemoradiotherapy (CRT), 30%–50% of patients with locally advanced cervical cancer relapse; however, there is a lack of prognostic biomarkers to identify patients at high risk of relapse. MONSTAR-SCREEN-3 is a prospective multicenter study targeting 1,100 patients with solid tumors across several indications undergoing curative-intent treatment, utilizing an ultrasensitive MRD test (Precise MRD). Here we report the interim results from the cervical cancer cohort.Materials/Methods:
Adult women with tumor size > 4 cm or FIGO stage IIB-IVA cervical cancer who underwent definitive chemoradiotherapy were included in this analysis. Precise MRD (Myriad Genetics), an ultrasensitive, tumor-informed assay targeting up to 1,000 patient-specific alterations identified through whole genome sequencing of tumor tissue, was used for ctDNA analysis at baseline, post-CRT, 1 month post-CRT, quarterly in year 1, and every 6 months thereafter for up to 2 years. Differences in baseline tumor fraction due to patient characteristics and the longitudinal MRD detection were evaluated.Results:
As of November 2025, 95 patients with cervical cancer were enrolled, of whom 82 were treated with definitive CRT. We analyzed 48 patients at 124 timepoints with both clinical data and ctDNA results available . Forty-three patients had squamous cell carcinoma, and 5 had adenocarcinoma. FIGO stages at initial diagnosis were II (27%), III (67%), and IV (6%). Customized panel creation succeeded in 47/48 patients (98%). The assay showed 100% baseline sensitivity (47/47), with 2% detected at ultrasensitive level (< 100 parts per million [ppm]). The ctDNA level was significantly higher in stage III-IV than in stage II (median tumor fraction [TF], 8762 vs. 1654 ppm, p=0.03) and significantly higher in squamous cell carcinoma than in adenocarcinoma (median TF, 7850 vs. 632 ppm, p=0.03), despite similar stage distribution (all adenocarcinoma and most squamous cell carcinoma were stage III). MRD positivity post-CRT, 1 month post-CRT, and 3 months post-CRT were 35% (9/26), 30% (8/27), and 33% (7/21), respectively (ultrasensitive level: 44%, 25%, and 14%, respectively). Three patients developed recurrence after CRT, all of whom were MRD-positive at 1-month post-CRT, with a median lead time of 2 months (range: 1.9-4.9), highlighting the potential clinical impact of earlier detection for recurrence.Conclusion:
These interim results demonstrate the successful implementation of a WGS-based personalized ultrasensitive ctDNA detection assay in cervical cancer. These findings support the potential clinical utility of this assay, though longer follow-up is needed to fully establish its role in cervical cancer management with definitive CRT.