Supplementary Figure S3 from 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

Slater, Susanna; Bryant, Annette; Aresu, Maria; Begum, Ruwaida; Chen, Hsiang-Chi; Peckitt, Clare; Lazaro-Alcausi, Retchel; Carter, Paul; Anandappa, Gayathri; Khakoo, Shelize; Melcher, Lucinda; Potter, Vanessa; Marti, Francisca M.; Huang, Joesph; Branagan, Graham; George, Nicol; Abulafi, Muti; Duff, Sarah; Raja, Ashraf; Gupta, Ashish; West, Nicholas; Bucheit, Leslie; Rich, Thereasa; Chau, Ian; Cunningham, David; Starling, Naureen

doi:10.1158/1078-0432.26710972.v1

Supplementary Figure S3 from 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

https://doi.org/10.1158/1078-0432.26710972

journal contribution

posted on 2024-08-15, 07:29 authored by Susanna Slater, Annette Bryant, Maria Aresu, Ruwaida Begum, Hsiang-Chi Chen, Clare Peckitt, Retchel Lazaro-Alcausi, Paul Carter, Gayathri Anandappa, Shelize Khakoo, Lucinda Melcher, Vanessa Potter, Francisca M. Marti, Joesph Huang, Graham Branagan, Nicol George, Muti Abulafi, Sarah Duff, Ashraf Raja, Ashish Gupta, Nicholas West, Leslie Bucheit, Thereasa Rich, Ian Chau, David Cunningham, Naureen Starling

<p>Sensitivity analysis for landmark and longitudinal analysis populations (n=33)</p>

Funding

NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research (BRC)

Royal Marsden Cancer Charity (The Royal Marsden Cancer Charity)

History

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DOI - Is supplement to 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

ARTICLE ABSTRACT

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. 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). 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). 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.