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dc.contributor.authorTie, Jeanne-
dc.contributor.authorCohen, Joshua D-
dc.contributor.authorLo, Serigne N-
dc.contributor.authorWang, Yuxuan-
dc.contributor.authorLi, Lu-
dc.contributor.authorChristie, Michael-
dc.contributor.authorLee, Margaret-
dc.contributor.authorWong, Rachel-
dc.contributor.authorKosmider, Suzanne-
dc.contributor.authorSkinner, Iain-
dc.contributor.authorWong, Hui Li-
dc.contributor.authorLee, Belinda-
dc.contributor.authorBurge, Matthew E-
dc.contributor.authorYip, Desmond-
dc.contributor.authorKarapetis, Christos S-
dc.contributor.authorPrice, Timothy J-
dc.contributor.authorTebbutt, Niall C-
dc.contributor.authorHaydon, Andrew M-
dc.contributor.authorPtak, Janine-
dc.contributor.authorSchaeffer, Mary J-
dc.contributor.authorSilliman, Natalie-
dc.contributor.authorDobbyn, Lisa-
dc.contributor.authorPopoli, Maria-
dc.contributor.authorTomasetti, Cristian-
dc.contributor.authorPapadopoulos, Nickolas-
dc.contributor.authorKinzler, Kenneth W-
dc.contributor.authorVogelstein, Bert-
dc.contributor.authorGibbs, Peter-
dc.identifier.citationInternational Journal of Cancer 2021; 148(4): 1014-1026en
dc.description.abstractStudies 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.en
dc.subjectcirculating tumor DNAen
dc.subjectcolorectal canceren
dc.titlePrognostic Significance of Post-Surgery Circulating Tumor DNA in Non-Metastatic Colorectal Cancer: Individual Patient Pooled Analysis of Three Cohort Studies.en
dc.typeJournal Articleen
dc.identifier.journaltitleInternational Journal of Canceren
dc.identifier.affiliationEastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australiaen
dc.identifier.affiliationLudwig Center and Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, USAen
dc.identifier.affiliationDepartment of Medical Oncology, Eastern Health, Melbourne, Australiaen
dc.identifier.affiliationDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USAen
dc.identifier.affiliationDivision of Biostatistics & Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, USAen
dc.identifier.affiliationDepartment of Pathology, Royal Melbourne Hospital, Melbourne, Australiaen
dc.identifier.affiliationInstitute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia..en
dc.identifier.affiliationFaculty of Medicine and Health, The University of Sydney, Sydney, Australiaen
dc.identifier.affiliationDivision of Personalised Oncology, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, The Alfred Hospital, Melbourne, Australiaen
dc.identifier.affiliationMedical Oncologyen
dc.identifier.affiliationDepartment of Medical Oncology, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Flinders Medical Centre, Flinders University, Adelaide, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Australian National University, Canberra, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australiaen
dc.identifier.affiliationMelanoma Institute Australia, The University of Sydney, North Sydney, Australiaen
dc.identifier.affiliationFaculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Western Health, Melbourne, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Wellness and Research Centreen
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