Abstract B04: Early detection of ovarian cancer recurrence using p53-mutated circulating tumor DNA as non-invasive biomarkers.

Abstract

Abstract Objectives: Epithelial ovarian cancer is the most lethal gynecologic cancer and it has a very high recurrence rate. Early detection of recurrence is very important as well as good treatment; however, the accuracy of CA-125 is approximately 50%. Circulating cell-free DNA (cfDNA) carrying tumor-specific somatic alterations, as called circulating tumor DNA (ctDNA), can be isolated from human body fluids. Recently, ctDNA is emerging as a new generation of non-invasive cancer biomarker Moreover ctDNA could be a more sensitive and specific biomarker than CA-125 in epithelial ovarian cancer. According to The Cancer Genome Atlas (TCGA) data, 95% of high-grade serous ovarian cancer (HGS-OC) has mutations in the p53 gene. This study is to investigate that p53-mutated ctDNA could be a biomarker for the early detection of recurrence comparing to CA-125 in HGS-OC. Procedures: We enrolled 85 patients with suspected ovarian cancer from July 2013 to June 2015 and 51 patients were epithelial ovarian cancer. We monitored the level of p53-mutated ctDNA compared with CA-125 in 25 of 38 patients (66%) with HGS-OC who were receiving surgery and continuing chemotherapy treatment. We used targeted-p53 whole exon sequencing to detect somatic genomic alterations from cancer tissue and used droplet digital polymerase chain reaction (ddPCR) to verify ctDNA in serially collected plasma samples. Results: We evaluated ctDNA levels as a monitoring method of the response to chemotherapy and tumor progression. We detected p53 mutations in 38 of 51 women (76%) by whole exon sequencing in cancer tissue and somatic genomic alteration of p53 showed in various sites. Ten of twenty-five (40%) patients who were monitored by ctDNA showed increasing levels of p53-mutated ctDNA during or after scheduled chemotherapy. Even though the ctDNA levels of these 10 patients were increased, the levels of CA-125 were still remained in normal range (under 35 Unit/mL). Especially, 3 patients, the disease progression was observed by imaging method after a few months after the increasing ctDNA. Conclusions: In conclusion, these data suggest that sequential monitoring of p53-mutated ctDNA may have potential as a sensitive and specific biomarker for early detection of recurrence in HGS-OC Citation Format: Ha-Young Lee, Shin-Wha Lee, Geum-Hee Na, Sang-Eun Lee, Dong-Woo Kang, Yong-Man Kim. Early detection of ovarian cancer recurrence using p53-mutated circulating tumor DNA as non-invasive biomarkers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B04.