학술논문
Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer.
Document Type
Article
Author
Hou, June Y.; Chapman, Jocelyn S.; Kalashnikova, Ekaterina; Pierson, William; Smith-McCune, Karen; Pineda, Geovanni; Vattakalam, Reena Marie; Ross, Alexandra; Mills, Meredith; Suarez, Carlos J.; Davis, Tracy; Edwards, Robert; Boisen, Michelle; Sawyer, Sarah; Wu, Hsin-Ta; Dashner, Scott; Aushev, Vasily N.; George, Giby V.; Malhotra, Meenakshi; Zimmermann, Bernhard
Source
Subject
*CIRCULATING tumor DNA
*OVARIAN epithelial cancer
*OVARIAN cancer
*ADJUVANT chemotherapy
*LEAD time (Supply chain management)
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Language
ISSN
0090-8258
Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. We examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for EOC by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance. Plasma samples were collected from patients with stage I-IV EOC. Cohort A included patients with pre-surgical samples (N = 44, median follow-up: 2.7 years), cohort B and C included: patients with serially collected post-surgically (N = 12) and, during surveillance (N = 13), respectively (median follow-up: 2 years). Plasma samples were analyzed using a tumor-informed, personalized multiplex-PCR NGS assay; ctDNA status and CA-125 levels were correlated with clinical features and outcomes. Genomic profiling was performed on the entire cohort and was consistent with that seen in TCGA. In cohort A, ctDNA-positivity was observed in 73% (32/44) of presurgical samples and was higher in high nuclear grade disease. In cohort B and C, ctDNA was only detected in patients who relapsed (100% sensitivity and specificity) and preceded radiological findings by an average of 10 months. The presence of ctDNA at a single timepoint after completion of surgery +/− adjuvant chemotherapy and serially during surveillance was a strong predictor of relapse (HR:17.6, p = 0.001 and p < 0.0001, respectively), while CA-125 positivity was not (p = 0.113 and p = 0.056). The presence of ctDNA post-surgically is highly prognostic of reduced recurrence-free survival. CtDNA outperformed CA-125 in identifying patients at highest risk of recurrence. These results suggest that monitoring ctDNA could be beneficial in clinical decision-making for EOC patients. • Post-surgical ctDNA detection is prognostic of reduced recurrence-free survival. • Post-surgically, ctDNA detected relapse with 100% sensitivity and specificity. • ctDNA detection preceded radiological findings by an average lead time of 10 months. • The presence of ctDNA and not CA-125 was a strong predictor of relapse. [ABSTRACT FROM AUTHOR]