1. Prognostic significance of postsurgery circulating tumor <scp>DNA</scp> in nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies
- Author
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Joshua D. Cohen, Lisa Dobbyn, Desmond Yip, Jeanne Tie, Maria Popoli, Peter Gibbs, Bert Vogelstein, Yuxuan Wang, Cristian Tomasetti, Iain Skinner, Janine Ptak, Kenneth W. Kinzler, Hui-Li Wong, Christos S. Karapetis, Natalie Silliman, Suzanne Kosmider, Nickolas Papadopoulos, Matthew Burge, Mary J. Schaeffer, Timothy J. Price, Rachel Wong, Lu Li, Andrew Haydon, Belinda Lee, Margaret Lee, Niall C. Tebbutt, Serigne Lo, and Michael Christie
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,Rectum ,Kaplan-Meier Estimate ,Article ,Circulating Tumor DNA ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Stage (cooking) ,Young adult ,Lung cancer ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Proportional hazards model ,business.industry ,Hazard ratio ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Female ,Neoplasm Recurrence, Local ,Colorectal Neoplasms ,business ,Cohort study - 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 nonmetastatic colorectal cancer (CRC). Plasma samples were collected 4 to 10 weeks after surgery. Mutations in ctDNA were assayed using a massively parallel sequencing technique called SafeSeqS. We analyzed 485 CRC patients (230 Stage II colon, 96 Stage III colon, and 159 locally advanced rectum). 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 = .740). ctDNA detection was associated with poorer 5-year recurrence-free (38.6% vs 85.5%; P < .001) and overall survival (64.6% vs 89.4%; P < .001). The predictive accuracy of postsurgery ctDNA for recurrence was higher than that of individual clinicopathologic risk features. Recurrence risk increased exponentially with increasing ctDNA mutant allele frequency (MAF) (hazard ratio, 1.2, 2.5 and 5.8 for MAF of 0.1%, 0.5% and 1%). Postsurgery ctDNA was detected in 3 of 20 (15%) patients with locoregional and 27 of 60 (45%) with distant recurrence (P = .018). This analysis demonstrates a consistent long-term impact of ctDNA as a prognostic marker across nonmetastatic CRC, where ctDNA outperforms other clinicopathologic risk factors and MAF further stratifies recurrence risk. ctDNA is a better predictor of distant vs locoregional recurrence.
- Published
- 2020