Jianjun Gao

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

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.

Treatment of advanced ovarian cancer with carboplatin and paclitaxel in a patient undergoing hemodialysis: Case report and literature review

AbstractA 69‐year‐old woman under maintenance hemodialysis was diagnosed with advanced ovarian cancer. We treated the patient with combination chemotherapy using paclitaxel and carboplatin. She experienced grade 4 thrombopenia on day 8 of the third course. The area under the concentration versus time curve (AUC) of platinum was 3.5 mg/ml·min. The interval between chemotherapy and hemodialysis was shortened starting with the fourth course. The AUC of platinum was then found to be 1.8 mg/ml·min. After seven courses of chemotherapy, the patient's CA 125 serum level dropped from 1317 to 42.6 U/ml. Nevertheless, the patient presented with long periods of severe myelosuppression. In patients on hemodialysis receiving such chemotherapy, the AUC of each cycle should be closely monitored and the dialysis schedule should be adjusted as need to reduce the risk of bone marrow suppression.