Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26426
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dc.contributor.authorTie, Jeanne-
dc.contributor.authorWang, Yuxuan-
dc.contributor.authorCohen, Joshua-
dc.contributor.authorLi, Lu-
dc.contributor.authorHong, Wei-
dc.contributor.authorChristie, Michael-
dc.contributor.authorWong, Hui Li-
dc.contributor.authorKosmider, Suzanne-
dc.contributor.authorWong, Rachel-
dc.contributor.authorThomson, Benjamin-
dc.contributor.authorChoi, Julian-
dc.contributor.authorFox, Adrian-
dc.contributor.authorField, Kathryn-
dc.contributor.authorBurge, Matthew-
dc.contributor.authorShannon, Jenny-
dc.contributor.authorKotasek, Dusan-
dc.contributor.authorTebbutt, Niall C-
dc.contributor.authorKarapetis, Christos-
dc.contributor.authorUnderhill, Craig-
dc.contributor.authorHaydon, Andrew-
dc.contributor.authorSchaeffer, Joy-
dc.contributor.authorPtak, Janine-
dc.contributor.authorTomasetti, Cristian-
dc.contributor.authorPapadopoulos, Nicholas-
dc.contributor.authorKinzler, Kenneth W-
dc.contributor.authorVogelstein, Bert-
dc.contributor.authorGibbs, Peter-
dc.date2021-05-03-
dc.date.accessioned2021-05-10T07:13:23Z-
dc.date.available2021-05-10T07:13:23Z-
dc.date.issued2021-05-03-
dc.identifier.citationPLoS Medicine 2021; 18(5): e1003620en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/26426-
dc.description.abstractIn patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study. We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing. We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM. ACTRN12612000345886.en
dc.language.isoeng-
dc.titleCirculating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.en
dc.typeJournal Articleen
dc.identifier.journaltitlePLoS Medicineen
dc.identifier.affiliationOlivia Newton-John Cancer Wellness and Research Centreen
dc.identifier.affiliationFlinders Medical Centre, Flinders University, Adelaide, Australiaen
dc.identifier.affiliationBorder Medical Oncology, Albury, Australiaen
dc.identifier.affiliationThe Alfred Hospital, Melbourne, Australiaen
dc.identifier.affiliationEastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australiaen
dc.identifier.affiliationEastern Health, Melbourne, Australiaen
dc.identifier.affiliationRoyal Melbourne Hospital, Melbourne, Australiaen
dc.identifier.affiliationSidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland, United States of Americaen
dc.identifier.affiliationPeter MacCallum Cancer Centre, Melbourne, Australiaen
dc.identifier.affiliationWestern Health, Melbourne, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australiaen
dc.identifier.affiliationFaculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australiaen
dc.identifier.affiliationJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of Americaen
dc.identifier.affiliationRoyal Brisbane and Women's Hospital, Brisbane, Australiaen
dc.identifier.affiliationNepean Cancer Care Centre, Sydney, Australiaen
dc.identifier.affiliationIcon Cancer Centre, Adelaide, Australiaen
dc.identifier.doi10.1371/journal.pmed.1003620en
dc.type.contentTexten
dc.identifier.orcid0000-0001-9244-2057en
dc.identifier.orcid0000-0003-1158-5668en
dc.identifier.orcid0000-0002-1920-4965en
dc.identifier.orcid0000-0002-9236-9790en
dc.identifier.orcid0000-0003-3803-2107en
dc.identifier.orcid0000-0002-8817-8799en
dc.identifier.orcid0000-0002-4926-5689en
dc.identifier.orcid0000-0001-9007-8845en
dc.identifier.orcid0000-0002-1143-9129en
dc.identifier.orcid0000-0001-9483-4994en
dc.identifier.orcid0000-0002-2170-3560en
dc.identifier.orcid0000-0001-9335-2678en
dc.identifier.orcid0000-0002-4631-5855en
dc.identifier.orcid0000-0003-1934-8739en
dc.identifier.orcid0000-0003-3277-4804en
dc.identifier.orcid0000-0001-7135-7451en
dc.identifier.orcid0000-0001-5591-1176en
dc.identifier.pubmedid33939694-
local.name.researcherTebbutt, Niall C
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
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