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dc.contributor.authorHamfjord, Julian
dc.contributor.authorGuren, Tormod Kyrre
dc.contributor.authorDajani, Olav
dc.contributor.authorJohansen, Julia Sidenius
dc.contributor.authorGlimelius, Bengt
dc.contributor.authorSorbye, Halfdan
dc.contributor.authorPfeiffer, Per
dc.contributor.authorLingjærde, Ole Christian
dc.contributor.authorTveit, Magne Kjell
dc.contributor.authorKure, Elin H.
dc.contributor.authorPallisgaard, Niels
dc.contributor.authorSpindler, Karen-Lise Garm
dc.date.accessioned2020-01-30T09:36:23Z
dc.date.available2020-01-30T09:36:23Z
dc.date.created2019-10-13T14:06:05Z
dc.date.issued2019
dc.identifier.citationAnnals of Oncology. 2019, 30 (7), 1088-1095.nb_NO
dc.identifier.issn0923-7534
dc.identifier.urihttp://hdl.handle.net/11250/2638800
dc.descriptionThis is an Open Access article under the CC-BY-NC-ND license.nb_NO
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.nb_NO
dc.language.isoengnb_NO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleTotal circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapynb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.rights.holder(c) The Author(s) 2019.nb_NO
dc.source.pagenumber1088-1095nb_NO
dc.source.volume30nb_NO
dc.source.journalAnnals of Oncologynb_NO
dc.source.issue7nb_NO
dc.identifier.doi10.1093/annonc/mdz139
dc.identifier.cristin1736747
cristin.unitcode222,58,1,0
cristin.unitnameInstitutt for natur, helse og miljø
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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