Abstract B041: Circulating tumor cells are associated with a shorter disease-free interval in patients with advanced high-grade serous carcinoma undergoing neoadjuvant chemotherapy followed by interval cytoreductive surgery

Abstract Introduction: Circulating tumor cells (CTCs) are rare cancer cells shed from primary or metastatic tumors into the circulation, offering a minimally invasive biomarker for prognostic monitoring. While serial CTC sampling is prognostically validated in breast, prostate, and colorectal cancers, its role in ovarian cancers is poorly understood. This study therefore explores the association between CTC presence and disease-free interval (DFI) in patients with advanced high-grade serous carcinoma (HGSC), the most common form of ovarian cancer. Methods: Blood samples were collected from 14 patients with FIGO (International Federation of Gynecology and Obstetrics) stage III or IV HGSC undergoing neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICRS). Peripheral samples were taken at two timepoints: pre-NACT (n = 14) and post-NACT (n = 12) (3-8 cycles, median: 4 cycles), prior to ICRS. An additional blood sample was collected intraoperatively from the ovarian vein during ICRS (n = 7), when deemed suitable by the surgeon. Whole blood was enriched on the Parsortix® PR1 microfluidic system. CTCs were identified using an optimized marker panel (EpCAM+, Cytokeratin(including CK7)+, Hoechst+, CD45-). Patients were stratified as CTC+ (if ≥1 CTC was detected at any timepoint) and CTC- (if no CTCs were detected throughout). Kaplan-Meier curves with log-rank tests were used to compare survival between groups. DFI was defined as the time from completion of first-line treatment to disease recurrence. Results CTCs were detected in 6/14 patients (43%) pre-NACT. Post-NACT, 3/12 (25%) were CTC+ (all pre-NACT positives). CTCs were detected in the ovarian vein at ICRS in 4/7 (57%) patients, including 3 with peripheral negativity. One patient was CTC+ pre-NACT and in the ovarian vein. After a median follow-up of 14 months, 11/14 (79%) patients had disease progression, 9 (82%) of whom were CTC+ at at least one timepoint. DFI was significantly shorter in CTC+ patients compared to CTC- patients (p = 0.0282, median DFI: 6 vs. 17 months). Discussion CTC presence was associated with reduced DFI in advanced HGSC patients undergoing NACT-ICRS. Despite the small sample size, this data suggests that serial CTC sampling may have prognostic value for longitudinal monitoring in HGSC and highlights the need for larger prospective trials to validate CTCs as a biomarker for prognosis. This research was supported by the North-South Research Programme administered by the Higher Education Authority on behalf of the Department of Further and Higher Education, Research, Innovation and Science, and the Shared Island Fund (CLuB: The All-Ireland Cancer Liquid Biopsies Consortium https://www.clubcancer.ie). Citation Format: Faye Lewis, Mark P. Ward, Feras Abu Saadeh, Catherine O'Gorman, Patrick J. Maguire, James P. Beirne, Waseem Kamran, Elzahra Ibrahim, Rebecca Hunter, Sinéad Hurley, Lucy Norris, Brian Henderson, Irene Narinda, Marika Kanjuga, Lorraine O'Driscoll, Kathy Gately, Volga M. Saini, Karen Cadoo, Cara Martin, John J. O'Leary, Sharon A. O'Toole. Circulating tumor cells are associated with a shorter disease-free interval in patients with advanced high-grade serous carcinoma undergoing neoadjuvant chemotherapy followed by interval cytoreductive surgery [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B041.