Surgical and Blood-Based Minimal Residual Disease in Patients with Ovarian Cancer after First-line Therapy: Clinical Outcomes and Translational Opportunities

作者：Anne Knisely, Yibo Dai, Graham L. Barlow, Sanghoon Lee, Barrett C. Lawson, Helen Clark, Bryan Fellman, Ying Yuan, Wei Lü, Idania Carolina Lubo Julio, Rossana N. Lazcano, Manoj Chelvanambi, Brenda Melendez, Bharat Singh, Bhavana Singh, Khalida Wani, Jianfeng Chen, Chih‐Chen Yeh, Jianjun Gao, Sean Barnes, Ou Shi, Khaja Khan, Alejandra G. Serrano, Lorena I. Gomez-Bolanos, Carly Bess Scalise, Samantha K. Cheung, Punashi Dutta, Sharlene Velichko, Adam C. ElNaggar, Minetta C. Liu, Roni Nitecki Wilke, Jeffrey How, Lois M. Ramondetta, David M. Boruta, Gwyn Richardson, Aaron Shafer, Shannon N. Westin, Travis T. Sims, Anil K. Sood, Pedro T. Ramirez, Alexander J. Lazar, Pamela T. Soliman, Karen H. Lu, Cara Haymaker, Luisa M. Solis Soto, Jennifer A. Wargo, Rachel N. Grisham, Kai W. Wucherpfennig, Linghua Wang, Amir A. Jazaeri · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-25-0512 · 被引用次数：10 · 研究领域：Ovarian cancer diagnosis and treatment、Single-cell and spatial transcriptomics、PARP inhibition in cancer therapy

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,...