Prognostic significance of post-surgery circulating tumor DNA in non-metastatic colorectal cancer: individual patient pooled analysis of three cohort studies
- Author(s)
- Tie, J; Cohen, JD; Lo, SN; Wang, Y; Li, L; Christie, M; Lee, M; Wong, R; Kosmider, S; Skinner, I; Wong, HL; Lee, B; Burge, ME; Yip, D; Karapetis, CS; Price, TJ; Tebbutt, NC; Haydon, AM; Ptak, J; Schaeffer, MJ; Silliman, N; Dobbyn, L; Popoli, M; Tomasetti, C; Papadopoulos, N; Kinzler, KW; Vogelstein, B; Gibbs, P;
- Details
- Publication Year 2021-02-15,Volume 148,Issue #4,Page 1014-1026. (epub 2020 Oct 6)
- Journal Title
- International Journal of Cancer
- Abstract
- Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined analysis of data across completed studies could further our understanding of circulating tumor DNA (ctDNA) as a prognostic marker and inform future trial design. We combined individual patient data from three independent cohort studies of non-metastatic colorectal cancer (CRC). Plasma samples were collected 4-10 weeks after surgery. Mutations in ctDNA were assayed using massively-parallel-sequencing with a technique called SafeSeqS. We analyzed 485 CRC patients (230 stage II colon, 96 stage III colon, 159 locally advanced rectal). ctDNA was detected after surgery in 59 (12%) patients overall (11.0%, 12.5% and 13.8% for samples taken at 4-6, 6-8 and 8-10 weeks; P=0.740). ctDNA detection was associated with poorer 5-year recurrence-free (38.6% vs 85.5%; P<0.001) and overall survival (64.6% vs 89.4%; P<0.001). The predictive accuracy of post-surgery ctDNA for recurrence was higher than that of individual clinico-pathological risk features. Recurrence risk increased exponentially with increasing ctDNA mutant allele fraction (MAF) (hazard ratio, 1.2, 2.5 and 5.8 for MAF of 0.1, 0.5 and 1%). Post-surgery ctDNA was detected in 3 of 20 (15%) patients with loco-regional and 27 of 60 (45%) with distant recurrence (P=0.018). This analysis demonstrates a consistent long-term impact of ctDNA as a prognostic marker across non-metastatic CRC, where ctDNA outperforms other clinico-pathological risk factors and MAF further stratifies recurrence risk. ctDNA is a better predictor of distant versus loco-regional recurrence. This article is protected by copyright. All rights reserved.
- Publisher
- Wiley
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 32984952
- Publisher's Version
- https://doi.org/10.1002/ijc.33312
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- Refer to copyright notice on published article.
Creation Date: 2020-10-02 02:01:50
Last Modified: 2021-10-21 10:55:06