Abstract LB-73: Circulating tumor cells with the invasive phenotype predict progression free survival and overall survival in preoperative patients diagnosed with advanced epithelial ovarian cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Purpose: Circulating tumor cells (CTCs) might function as prognostic markers for monitoring and assessing therapy efficacy ex vivo . This study aimed to measure overall population of CTCs based on expression of epithelial lineage (Epi) markers and the subpopulation of CTCs with the invasive phenotype (iCTCs) in preoperative patients for prognosis of advanced Epithelial Ovarian Cancer (EOC). Experimental Design: CTCs and iCTCs enriched by the Cell Adhesion Matrix (CAM)-coated devices from 122 preoperative patients were identified as Epi+ nucleic acid (NA)+ hematopoietic lineage (HL)- cells and CAM uptake (CAM+) Epi+ NA+ HL- cells, respectively. CTCs and iCTCs were enumerated using multiplex flow cytometry, validated by microscopy, and correlated with overall survival (OS) and progression-free survival (PFS). Results: iCTCs were detected in 0/39 (0%) benign patients, 5/11 (45.5%) Stage I, 2/4 (50%) Stage II, 41/43 (95.3%) Stage III and 16/16 (100%) stage IV patients (P-value <0.001). However, healthy (n=48) and benign women had noticeable CTCs (mean=10 and 3 CTCs/1.0-mL blood, respectively), and large variation (IQR=24.5 and 30 CTCs/1.0-mL blood, respectively), although CTCs were significantly different across different stage groups. Kaplan-Meier estimates of OS at 5 years in the iCTC positive and negative groups were 15.4% (95% CI, 7.2% to 26.3%) and 94% (95% CI, 82.5% to 98%), respectively. The PFS in the iCTC positive group was also significantly lower than that in the negative group (P-value <0.001). In multivariable Cox models, iCTCs were independently predictive of OS (P-value <0.001) and provided predictive power for disease recurrence independent of diagnostic disease stages, age, debulking status and platinum sensitivity. Conclusion: CTCs show the expression of heterogeneous epithelial antigens with potential biologic relevance. Co-expression of epithelial antigens and invasiveness of iCTCs in preoperative patients provides prognosis of advanced EOC that could help tailor appropriate therapy. Citation Format: Wen-Tien Chen, Qiang Zhao, Huan Dong, Jie Yang, Qiao Zhang, Tina Fan, Marc G. Golightly, Whitney C. Dessio, Stefan Madajewicz, Melissa Henretta, Michael L. Pearl. Circulating tumor cells with the invasive phenotype predict progression free survival and overall survival in preoperative patients diagnosed with advanced epithelial ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-73. doi:10.1158/1538-7445.AM2013-LB-73