Abstract
Kinetics of postoperative circulating cell-free DNA and impact on minimal residual disease detection rates in patients with resected stage I-III colorectal cancer
Journal of clinical oncology, Vol.41(4_suppl), pp.5-5
02/01/2023
DOI: 10.1200/JCO.2023.41.4_suppl.5
Abstract
5 Background: A growing body of evidence supports the utility of circulating tumor DNA (ctDNA) as a useful biomarker for detecting molecular residual disease (MRD) in colorectal cancer (CRC). Immediately after surgery or during adjuvant therapy, high levels of cell-free DNA (cfDNA) from normal tissue may limit the detection of tumor-derived ctDNA. The optimal timing of blood collection for reliable MRD detection after surgery or adjuvant therapy remains unclear. Methods: In this retrospective, U.S.-based, multi-institutional study, data from commercial ctDNA testing in 16,347 patients with stage I-III CRC were analyzed. Complete clinical data were available for 417 patients with 2,538 plasma samples collected between 6/2019 and 4/2022. The median follow-up for relapsed and non-relapsed patients was 730 and 615 days, respectively. A personalized, tumor-informed multiplex PCR-based next-generation sequencing assay (Signatera) was used to quantify ctDNA prior to surgery and postoperatively in a longitudinal manner. We analyzed the kinetics of total cfDNA and compared it with the ctDNA MRD positivity rates at various time points after surgery. Results: Among all patients, cfDNA levels were higher immediately after surgery (0-2 weeks) and gradually declined during the subsequent 2-8 weeks (p<0.0001). Despite the higher cfDNA levels, among patients with immediate post-operative draws (0-2 weeks) 30.6% (113/369) of patients were ctDNA positive. Similar ctDNA detection rates were observed with conventional MRD windows after resection, whether the window was defined as 2-6 weeks (20.8%; 957/4605) or 2-8 weeks (20.9%; 1155/5534). In the clinically annotated cohort, ctDNA-positivity during the MRD time window of 2-8 weeks and during surveillance (>6 months post-operatively and subsequent to any adjuvant therapy) was significantly associated with worse recurrence-free survival as compared to ctDNA negative patients (MRD: HR 14.1, 95% CI: 5.8-34; p<0.0001; and surveillance HR 20.6, 95% CI: 10.6-37.6; p<0.0001), respectively. On analyzing cfDNA dynamics during adjuvant therapy, cfDNA levels gradually increased between 8 weeks and 8 months after surgery (p=0.0001), suggesting a potential impact of treatment on cell death and cfDNA shed. Conclusions: This is one of the first, large-scale in-depth studies evaluating treatment-based fluctuations in post-operative cfDNA and its correlation with ctDNA-positivity. Our analyses demonstrated no significant impact of plasma cfDNA levels on ctDNA detection rates across different MRD windows using a tumor-informed approach. This may affect real-world application of personalized ctDNA testing by allowing earlier testing windows, as well as guide clinical trial designs using ctDNA as an integral biomarker.
Details
- Title: Subtitle
- Kinetics of postoperative circulating cell-free DNA and impact on minimal residual disease detection rates in patients with resected stage I-III colorectal cancer
- Creators
- Stacey A. Cohen - Fred Hutch Cancer CenterPashtoon Murtaza Kasi - NewYork–Presbyterian HospitalVasily N. Aushev - NateraDiana L. Hanna - USC Norris Comprehensive Cancer CenterGregory P. Botta - University of California, San DiegoSaima Sharif - University of IowaVivek R. Sharma - James Graham Brown FoundationGeorgios I Laliotis - NateraAli Alqahtani - Georgetown University Medical CenterSreenivasa R Chandana - Cancer & Hematology Centers of Western Michigan, Grand Rapids, MI;Sandra Kang - Emory UniversitySakti Chakrabarti - Medical College of WisconsinBradley G. Somer - West Cancer CenterAnup Kasi - University of Kansas Medical CenterFarshid Dayyani - University of California, IrvineMidhun Malla - West Virginia UniversityAdham A Jurdi - NateraMinetta C. Liu - NateraAlexey Aleshin - NateraScott Kopetz - The University of Texas MD Anderson Cancer Center
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.41(4_suppl), pp.5-5
- DOI
- 10.1200/JCO.2023.41.4_suppl.5
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: None.
- Language
- English
- Date published
- 02/01/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363179702771
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