1. 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.
- Author
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Slater S, Bryant A, Aresu M, Begum R, Chen HC, 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, and Starling N
- Subjects
- Humans, Male, Female, Liquid Biopsy methods, Aged, Middle Aged, Prospective Studies, Adult, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local diagnosis, Neoplasm Staging, United Kingdom, Aged, 80 and over, Genomics methods, Mutation, Prognosis, Neoplasm, Residual genetics, Neoplasm, Residual diagnosis, Colorectal Neoplasms genetics, Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology, Colorectal Neoplasms blood, Colorectal Neoplasms surgery, DNA Methylation, Circulating Tumor DNA genetics, Circulating Tumor DNA blood, Biomarkers, Tumor genetics
- 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., (©2024 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2024
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