Abstract 552: Circulating tumor DNA predicts disease recurrence in ovarian cancer patients
Authors: Chapman Jocelyn S. , Pierson William E. , Smith-McCune Karen , Pineda Geovanni , Vattakalam Reena M. , Ross Alexandra , Mills Meredith A. , Suarez Carlos J. , Davis Tracy , Edwards Robert P. , Boisen Michelle , Ford James M. , Hou June Y. , Wu Hsin-Ta , Dashner Scott , Kalashnikova Ekaterina , Rodriguez Angel , Zimmermann Bernhard , Sawyer Sarah , Sethi Himanshu , Aleshin Alexey 
Published: July 2021

Abstract
Introduction: Epithelial ovarian, fallopian tube, and peritoneal cancer (EOC) is the most lethal gynecologic malignancy with a 5-year survival rate of 47%. While primary treatment generally results in remission, most patients relapse within 3 years. CA-125 is a commonly used biomarker for recurrence detection, however, it lacks specificity and is not associated with improved survival. Here we examine the utility of circulating tumor DNA (ctDNA) as a biomarker for EOC by assessing its relationship to patient outcome and CA-125 when measured pre-surgically and during patient monitoring.
Methods: This study included patients diagnosed with stage I-IV EOC with plasma samples collected pre-surgically (n=44) and a group of patients (n=22) with serially collected samples after surgery. Median follow-up for patients with pre-surgical samples and with prospectively collected samples was 29 months (range: 6-150) and 15 months (range: 0.6-26), respectively. Whole exome sequencing was performed on patient tumors and matched normal tissue to design patient-specific ctDNA assays (bespoke mPCR NGS assay) for variant detection in plasma samples. The relationship between ctDNA status, CA-125 levels, and recurrence-free survival (RFS) were evaluated (Fisher's exact, log-rank test).
Results: Among patients with presurgical plasma samples high-grade serous was the most common histological subtype 66% (29/44). Endometrioid represented 11% (5/44) of tumors and 23% (10/44) were tumors of other epithelial subtypes. In this cohort 75% (33/44) had early-stage disease, 7% (3/44) were metastatic and 18% (8/44) had the unstaged disease. The presence of ctDNA was observed in 73% of samples at baseline with detection rates of 69% (20/29) for serous and 80% (4/5) for endometrioid histologies. Pre-surgical ctDNA detection was significantly associated with a higher grade (p=0.003). All patients with ctDNA negative status at baseline (n=12) survived until the end of follow-up (median: 25 months), while 3 deaths were observed among ctDNA positive patients (n=32; p=0.003).
In the sub-cohort of patients with prospective post-surgical plasma collection, ctDNA was observed in samples of all patients who relapsed (7/7; 100% sensitivity). ctDNA detection preceded radiological findings by a median of 9 months (range: 2-36). None of the patients with ctDNA negative status within 6 months after enrollment experienced disease progression (13/13; 100% specificity). The presence of ctDNA was observed to be a strong predictor of relapse (HR: 12.75, 95%CI: 1.7-94 p&lt;0.0001), while CA-125 was not significantly associated with RFS (HR: 1.3, 95%CI: 0.3-6.3; p=0.09).
Conclusions: The presence of ctDNA post-surgically is highly prognostic of decreased RFS and was found to be a stronger predictor of disease progression than CA-125 monitoring. These results suggest that monitoring ctDNA could be a useful tool in clinical decision making for patients with EOC.
Citation Format: Jocelyn S. Chapman, William E. Pierson, Karen Smith-McCune, Geovanni Pineda, Reena M. Vattakalam, Alexandra Ross, Meredith A. Mills, Carlos J. Suarez, Tracy Davis, Robert P. Edwards, Michelle Boisen, James M. Ford, June Y. Hou, Hsin-Ta Wu, Scott Dashner, Ekaterina Kalashnikova, Angel Rodriguez, Bernhard Zimmermann, Sarah Sawyer, Himanshu Sethi, Alexey Aleshin. Circulating tumor DNA predicts disease recurrence in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 552.