Concordance of circulating tumor DNA and tissue genomic profiling in ovarian cancer: Influencing factors and clinical significance.

5548 Background: Next-generation sequencing of plasma circulating tumor DNA (ctDNA) shows promise in ovarian cancer management as a minimally invasive alternative to tissue sequencing. However, concordance between genomic alterations detected in tissue and ctDNA remains incompletely characterized, with limited understanding of influencing factors and clinical implications. Methods: We analyzed 29 matched pretreatment tissue and plasma samples from treatment-naïve ovarian cancer patients using a customized 2365-gene panel. Overall and individual concordance rates were calculated as the ratio of total concordant mutations to total tissue mutations, with patients stratified into high concordance (≥50%) and poor concordance (<50%) groups. Clinicopathological and tumor molecular factors influencing concordance were analyzed. Relationship between concordance rates and clinical outcomes, including chemosensitivity (KELIM score) and progression-free survival (PFS), was assessed in advanced-stage patients. Results: The cohort predominantly comprised FIGO III-IV disease (89.7%) and high-grade serous histology (89.7%), with median follow-up of 306 (66-570) days. Overall tissue-plasma concordance rate was 42%, with shared variants exhibiting identical abundance patterns across sample types (r=0.25, p =0.0074) and encompassing 66.1% of tissue driver mutations. Tissue-specific mutations displayed lower variant allele frequencies than shared mutations (median 4.4% vs 28.7%). Single nucleotide variants showed higher plasma detection rate than structural variants (47.3% vs 25.4%). Individual concordance rates varied substantially (0-83.3%). High concordance group exhibited higher tumor Ki-67 index (median 85% vs 70%), tissue tumor mutation burden (TMB, median 5.1 vs 4.1 muts/Mb), and plasma ctDNA fraction (median 8.1% vs 0.9%). No significant differences were observed in largest tumor diameter, CA125 levels, tumor sample locations (from primary site or metastatic site), or BRCA mutation/homologous recombination status between groups. By multivariable analysis, higher TMB (OR 1.931, 95% CI 1.064-3.504) and plasma ctDNA fraction (OR 1.416, 95% CI 1.060-1.893) independently associated with high concordance rates. In advanced-stage patients, poor concordance group showed lower KELIM scores (median 0.7 vs 1.2; 15.4% vs 69.2% of patients with score ≥1), indicating reduced chemosensitivity. Concordance rates strongly correlated with KELIM scores (r=0.71, p <0.0001). Poor concordance group demonstrated shorter PFS (median 436 days vs not reached, p =0.037). Conclusions: Our study revealed moderate concordance between pretreatment tumor tissue and plasma ctDNA mutation profiles in ovarian cancer, influenced by technical and biological factors. Tissue-plasma concordance may serve as a novel chemosensitivity and prognostic indicator.