Faculty, Staff and Student Publications

Language

English

Publication Date

10-1-2025

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-25-0512

PMID

40748258

PMCID

PMC12485385

PubMedCentral® Full Text Version

Post-print

Abstract

Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy.

Experimental design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients.

Results: Forty of 95 (42.1%) patients had surgically detected MRD, which was associated with worse PFS (median PFS 7.4 vs. 23.8 months; P < 0.001) and OS (median OS 33.9 vs. not reached; P < 0.001). SLL positivity was an independent negative prognostic factor for OS (HR, 4.40; 95% confidence interval, 1.37-14.21; P = 0.013) in multivariable analysis. Among 44 patients who underwent SLL and had ctDNA testing, 34% (15/44) were ctDNA-positive, which was associated with worse PFS (6.4 vs. 28.1 months; P < 0.001) and OS (32.4 months vs. not reached; P = 0.008). We demonstrated the feasibility of spatial multiomics in studying MRD and their ability to provide hypothesis-generating observations, implicating the upregulation of the hypoxia signaling pathway, expression of multiple druggable targets (CDK6, GLS, MSLN, ERBB2), and immune exclusion in MRD lesions.

Conclusions: Approximately half of patients in clinical remission after first-line therapy have assessable MRD, which can inform prognosis, therapeutic target discovery, and clinical trials.

Keywords

Humans, Female, Neoplasm, Residual, Middle Aged, Ovarian Neoplasms, Aged, Circulating Tumor DNA, Biomarkers, Tumor, Prognosis, Adult, Carcinoma, Ovarian Epithelial, Aged, 80 and over, Treatment Outcome

Published Open-Access

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