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Abstract 552: Circulating tumor DNA predicts disease recurrence in ovarian cancer patients

2021; American Association for Cancer Research; Volume: 81; Issue: 13_Supplement Linguagem: Inglês

10.1158/1538-7445.am2021-552

1538-7445

Jocelyn Chapman, William E. Pierson, Karen Smith‐McCune, Geovanni Pineda, Reena M. Vattakalam, Alexandra Ross, Meredith Mills, Carlos J. Suarez, Thomas P. Davis, Robert P. Edwards, M.M. Boisen, James M. Ford, June Y. Hou, Hsin-Ta Wu, Scott Dashner, Ekaterina Kalashnikova, Angel Rodriguez, Bernhard Zimmermann, Sarah Sawyer, Himanshu Sethi, Alexey Aleshin,

Cancer Cells and Metastasis

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<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.