Abstract AP06: SUBCLINICAL SIGNIFICANCE OF CIRCULATING TUMOR CELLS IN EPITHELIAL OVARIAN CANCER AS AN EARLY INDICATEOR OF RECURRENCE

Abstract

Abstract BACKGROUND: After diagnosis of cancer and subsequent treatment, a fraction of epithelial ovarian cancer (EOC) patients relapse with distant metastatic disease. While the fraction of the treated population that will relapse is predictable, there is not yet a way to determine the specific cases that will become metastatic. This transition between localized and disseminated cancer is clinically identified by the appearance of the patient's original cancer in a new anatomic location by various imaging methodologies or the increase of surrogate serum biomarkers. The actual biologic transition point, however, clearly occurs at some point prior to the time when metastasis becomes clinically evident. This becomes relevant during periods when disease is not clinically evident, where more sensitive identification methods of relapsing cancer may offer opportunities for therapy before tumor burden rises to an incurable level. PURPOSE: With the observation that circulating tumor cells (CTCs) are found in cancer patients with no clinical evidence of disseminated disease prior to clinically evident relapse, we sought to investigate whether the presence of CTCs in the circulatory compartment could possibly indicate tumor dissemination at its earliest time point and whether that could be leveraged to develop predictive models and markers that identify patients prior to clinical evidence of recurrent disease. METHODS: Peripheral blood samples collected after chemotherapy from 18 patients diagnosed with serous EOC were evaluated using the High Definition– Single Cell Assay (HD–SCA) for HD–CTCs enumeration, cytomorphological analysis and DNA copy number variation (CNV) profiling. RESULTS: HD–CTCs (≥1 CTC/mL) were detected in 9 (50%) of these patients, 3 of whom relapsed. Despite the genomic heterogeneity of the CTCs analyzed, single cell CNV profiles from one of these recurrent patients showed clonal cyclin E1 amplification on chromosome 19 and ARID1A tumor suppressor gene deletion on chromosome 1, genomic alterations consistent with EOC. CONCLUSION: The data suggests malignancy of multiple, single CTCs in recurrent patients, and further analysis of CTCs from non–recurrent patients could provide the means to determine the subclinical significance of CTCs in ovarian cancer. Earlier diagnosis of relapse, and subsequent personalized treatment, could eventually lead to more favorable prognoses in EOC patients. Citation Format: Carmen Ruiz, Serena Zheng, Bridgette Duggan, James Hicks and Peter Kuhn. SUBCLINICAL SIGNIFICANCE OF CIRCULATING TUMOR CELLS IN EPITHELIAL OVARIAN CANCER AS AN EARLY INDICATEOR OF RECURRENCE [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP06.