dc.contributor.author | Slater, S | |
dc.contributor.author | Bryant, A | |
dc.contributor.author | Aresu, M | |
dc.contributor.author | Begum, R | |
dc.contributor.author | Chen, H-C | |
dc.contributor.author | Peckitt, C | |
dc.contributor.author | Lazaro-Alcausi, R | |
dc.contributor.author | Carter, P | |
dc.contributor.author | Anandappa, G | |
dc.contributor.author | Khakoo, S | |
dc.contributor.author | Melcher, L | |
dc.contributor.author | Potter, V | |
dc.contributor.author | Marti, FM | |
dc.contributor.author | Huang, J | |
dc.contributor.author | Branagan, G | |
dc.contributor.author | George, N | |
dc.contributor.author | Abulafi, M | |
dc.contributor.author | Duff, S | |
dc.contributor.author | Raja, A | |
dc.contributor.author | Gupta, A | |
dc.contributor.author | West, N | |
dc.contributor.author | Bucheit, L | |
dc.contributor.author | Rich, T | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Starling, N | |
dc.contributor.author | TRACC Part B trial investigators, | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-09-06T10:38:38Z | |
dc.date.available | 2024-09-06T10:38:38Z | |
dc.date.issued | 2024-08-15 | |
dc.identifier | 745904 | |
dc.identifier.citation | Clinical Cancer Research, 2024, 30 (16), pp. 3459 - 3469 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6381 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-24-0226 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-24-0226 | |
dc.description.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. | |
dc.format | Print | |
dc.format.extent | 3459 - 3469 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Humans | |
dc.subject | Neoplasm, Residual | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Male | |
dc.subject | Female | |
dc.subject | Liquid Biopsy | |
dc.subject | Aged | |
dc.subject | DNA Methylation | |
dc.subject | Middle Aged | |
dc.subject | Circulating Tumor DNA | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Prospective Studies | |
dc.subject | Adult | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Neoplasm Staging | |
dc.subject | United Kingdom | |
dc.subject | Aged, 80 and over | |
dc.subject | Genomics | |
dc.subject | Mutation | |
dc.subject | Prognosis | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-06-05 | |
dc.date.updated | 2024-09-06T10:37:47Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-24-0226 | |
rioxxterms.licenseref.startdate | 2024-08-15 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38864835 | |
pubs.issue | 16 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.) | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-24-0226 | |
pubs.volume | 30 | |
icr.researchteam | GI Clinical Trials | |
icr.researchteam | Medicine (RMH) | |
dc.contributor.icrauthor | Slater, Susanna | |
icr.provenance | Deposited by Mr Arek Surman on 2024-09-06. Deposit type is initial. No. of files: 1. Files: Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients wit.pdf | |