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dc.contributor.authorHamfjord, Julianen_US
dc.contributor.authorGuren, Tormod Kyrreen_US
dc.contributor.authorDajani, Olaven_US
dc.contributor.authorJohansen, Julia Sideniusen_US
dc.contributor.authorGlimelius, Bengten_US
dc.contributor.authorSorbye, Halfdanen_US
dc.contributor.authorPfeiffer, Peren_US
dc.contributor.authorLingjærde, Ole Christianen_US
dc.contributor.authorTveit, Magne Kjellen_US
dc.contributor.authorKure, Elin Wenche Heglanden_US
dc.contributor.authorPallisgaard, Nielsen_US
dc.contributor.authorSpindler, Karen-Lise Garmen_US
dc.PublishedHamfjord J, Guren TK, Dajani O, Johansen JS, et al. Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy. Annals of Oncology. 2019;30(7):1088-1095eng
dc.description.abstractBackground: Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors. Patients and methods: This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall survival (OS). Results: cfDNA was quantified in 493 patients, 54 were excluded mainly due to lymphocyte contamination. Median cfDNA level was 7673 alleles/ml (1050–1 645 000) for B2M and 5959 alleles/ml (555–854 167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6 months for levels above ULN and 25.9 months for levels below ULN (hazard ratio = 1.83, 95% confidence interval 1.51–2.21, P < 0.001). The result was confirmed in multivariate OS analysis adjusting for established clinicopathological characteristics. A linear regression model predicted cfDNA levels from sum of longest tumor diameters by RECIST, the presence of liver metastases and systemic inflammatory response as measured by interleukin 6 (F(6, 357) = 62.7, P < 0.001). Conclusion: cfDNA holds promise as a minimally invasive and clinically relevant prognostic biomarker in mCRC before initiating first-line oxaliplatin-based chemotherapy and may be a complex entity associated with tumor burden, liver metastases and systemic inflammatory response.en_US
dc.publisherElsevier Ltdeng
dc.rightsAttribution CC BY-NC-NDeng
dc.subjectcolorectal cancereng
dc.subjectcirculating cell-free DNAeng
dc.subjectinterleukin 6eng
dc.subjectprognostic biomarkereng
dc.titleTotal circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapyen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Author(s)
dc.source.journalAnnals of Oncology

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