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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, S. Bryant, A. Aresu, M. Begum, R. Chen, H. C. Peckitt, C. Lazaro-Alcausi, R. Carter, P. Anandappa, G. Khakoo, S.
Slater, S.
Bryant, A.
Aresu, M.
Begum, R.
Chen, H. C.
Peckitt, C.
Lazaro-Alcausi, R.
Carter, P.
Anandappa, G.
Khakoo, S.
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Abstract
PURPOSE: Absence of post-operative circulating tumour DNA (ctDNA) identifies resected colorectal cancer (CRC) patients with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. We present the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. DESIGN: TRACC included stage I-III resectable CRC patients. Prospective longitudinal plasma collection for ctDNA occurred pre- and post-surgery, post-ACT, every 3m for year 1 and every 6m in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2yr recurrence free survival (RFS) by post-operative ctDNA detection. (NCT04050345) Results: Between December 2016 and August 2022, 1203 were patients enrolled. Plasma samples (n=997) from 214 patients were analysed. 143 patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; 2 (1.4%) stage I, 64 (44.8%) stage II, 77 (53.8%) stage III. Median follow-up was 30.3m (95% CI: 29.5-31.3). 2yr RFS was 91.1% in patients with ctDNA not detected post-operatively 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. Median lead-time from ctDNA detection to radiological recurrence was 7.3m (IQR 3.3-12.5; n=9). CONCLUSIONS: Tissue-free MRD detection with longitudinal sampling predicts recurrence in stage I-III CRC without need for tissue sequencing. NPV is high supporting ACT de-escalation in patients with ctDNA not detected post-operatively, now being investigated in the UK TRACC Part C study.
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 Marti, Francisca
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.
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 Marti, Francisca
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.
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Date
2024
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Article
Citation
Slater S, Bryant A, Aresu M, Begum R, Chen HC, Peckitt C, et al. 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. Clinical cancer research : an official journal of the American Association for Cancer Research. 2024 Jun 12.