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.
Date
2024-08-15ICR Author
Author
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,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Neoplasm, Residual
Colorectal Neoplasms
Male
Female
Liquid Biopsy
Aged
DNA Methylation
Middle Aged
Circulating Tumor DNA
Biomarkers, Tumor
Prospective Studies
Adult
Neoplasm Recurrence, Local
Neoplasm Staging
United Kingdom
Aged, 80 and over
Genomics
Mutation
Prognosis
Research team
GI Clinical Trials
Medicine (RMH)
Language
eng
Date accepted
2024-06-05
License start date
2024-08-15
Citation
Clinical Cancer Research, 2024, 30 (16), pp. 3459 - 3469
Publisher
AMER ASSOC CANCER RESEARCH