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Title: Prognostic Significance of Post-Surgery Circulating Tumor DNA in Non-Metastatic Colorectal Cancer: Individual Patient Pooled Analysis of Three Cohort Studies.
Austin Authors: Tie, Jeanne;Cohen, Joshua D;Lo, Serigne N;Wang, Yuxuan;Li, Lu;Christie, Michael;Lee, Margaret;Wong, Rachel;Kosmider, Suzanne;Skinner, Iain;Wong, Hui Li;Lee, Belinda;Burge, Matthew E;Yip, Desmond;Karapetis, Christos S;Price, Timothy J;Tebbutt, Niall C ;Haydon, Andrew M;Ptak, Janine;Schaeffer, Mary J;Silliman, Natalie;Dobbyn, Lisa;Popoli, Maria;Tomasetti, Cristian;Papadopoulos, Nickolas;Kinzler, Kenneth W;Vogelstein, Bert;Gibbs, Peter
Affiliation: Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
Ludwig Center and Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, USA
Department of Medical Oncology, Eastern Health, Melbourne, Australia
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA
Division of Biostatistics & Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, USA
Department of Pathology, Royal Melbourne Hospital, Melbourne, Australia
Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia..
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Division of Personalised Oncology, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Department of Medical Oncology, The Alfred Hospital, Melbourne, Australia
Medical Oncology
Department of Medical Oncology, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia
Department of Medical Oncology, Flinders Medical Centre, Flinders University, Adelaide, Australia
Department of Medical Oncology, Australian National University, Canberra, Australia
Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia
Melanoma Institute Australia, The University of Sydney, North Sydney, Australia
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Department of Medical Oncology, Western Health, Melbourne, Australia
Olivia Newton-John Cancer Wellness and Research Centre
Issue Date: 15-Feb-2021 2020-09-27
Publication information: International Journal of Cancer 2021; 148(4): 1014-1026
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.
DOI: 10.1002/ijc.33312
ORCID: 0000-0001-9244-2057
PubMed URL: 32984952
Type: Journal Article
Subjects: circulating tumor DNA
colorectal cancer
Appears in Collections:Journal articles

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