Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study.
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Embargo End Date
ICR Authors
Authors
Slater, S
Bryant, A
Aresu, M
Begum, R
Chen, H-C
Peckitt, C
Lazaro-Alcausi, R
Carter, P
Anandappa, G
Khakoo, S
Melcher, L
Potter, V
Marti, FM
Huang, J
Branagan, G
George, N
Abulafi, M
Duff, S
Raja, A
Gupta, A
West, N
Bucheit, L
Rich, T
Chau, I
Cunningham, D
Starling, N
TRACC Part B trial investigators,
Bryant, A
Aresu, M
Begum, R
Chen, H-C
Peckitt, C
Lazaro-Alcausi, R
Carter, P
Anandappa, G
Khakoo, S
Melcher, L
Potter, V
Marti, FM
Huang, J
Branagan, G
George, N
Abulafi, M
Duff, S
Raja, A
Gupta, A
West, N
Bucheit, L
Rich, T
Chau, I
Cunningham, D
Starling, N
TRACC Part B trial investigators,
Document Type
Journal Article
Date
2024-08-15
Date Accepted
2024-06-05
Abstract
PURPOSE: The absence of postoperative circulating tumor DNA (ctDNA) identifies patients with resected colorectal cancer (CRC) with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. Our study presents the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. EXPERIMENTAL DESIGN: TRACC (tracking mutations in cell-free tumor DNA to predict relapse in early colorectal cancer) included patients with stage I to III resectable CRC. Prospective longitudinal plasma collection for ctDNA occurred pre- and postsurgery, post-ACT, every 3 months for year 1 and every 6 months in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2-year recurrence-free survival (RFS) by postoperative ctDNA detection (NCT04050345). RESULTS: Between December 2016 and August 2022, 1,203 were patients enrolled. Plasma samples (n = 997) from 214 patients were analyzed. One hundred forty-three patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; two (1.4%) stage I, 64 (44.8%) stage II, and 77 (53.8%) stage III. Median follow-up was 30.3 months (95% CI, 29.5-31.3). Two-year RFS was 91.1% in patients with ctDNA not detected postoperatively and 50.4% in those with ctDNA detected [HR, 6.5 (2.96-14.5); P < 0.0001]. Landmark negative predictive value (NPV) was 91.2% (95% CI, 83.9-95.9). Longitudinal sensitivity and specificity were 62.1% (95% CI, 42.2-79.3) and 85.9% (95% CI, 78.9-91.3), respectively. The median lead time from ctDNA detection to radiological recurrence was 7.3 months (IQR, 3.3-12.5; n = 9). CONCLUSIONS: Tissue-free MRD detection with longitudinal sampling predicts recurrence in patients with stage I to III CRC without the need for tissue sequencing. The UK TRACC Part C study is currently investigating the potential for ACT de-escalation in patients with undetectable postoperative ctDNA, given the high NPV indicating a low likelihood of residual disease.
Citation
Clinical Cancer Research, 2024, 30 (16), pp. 3459 - 3469
Source Title
Clinical Cancer Research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1078-0432
eISSN
1557-3265
1557-3265
1557-3265
Collections
Research Team
GI Clinical Trials
Medicine (RMH)
Medicine (RMH)