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Total circulating c...
Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy
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- Hamfjord, J. (författare)
- Oslo Univ Hosp, Dept Oncol, N-0407 Oslo, Norway;Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway
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- Guren, T. K. (författare)
- Oslo Univ Hosp, Dept Oncol, N-0407 Oslo, Norway;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway
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- Dajani, O. (författare)
- Oslo Univ Hosp, Dept Oncol, N-0407 Oslo, Norway
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- Johansen, J. S. (författare)
- Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Oncol, Herlev, Denmark
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- Glimelius, Bengt (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Sorbye, H. (författare)
- Haukeland Hosp, Dept Oncol, Bergen, Norway;Univ Bergen, Dept Clin Sci, Bergen, Norway
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- Pfeiffer, P. (författare)
- Odense Univ Hosp, Dept Oncol, Odense, Denmark;Univ Southern Denmark, Inst Clin Res, Odense, Denmark
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- Lingjaerde, O. C. (författare)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway;Univ Oslo, Dept Comp Sci, Oslo, Norway
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- Tveit, K. M. (författare)
- Oslo Univ Hosp, Dept Oncol, N-0407 Oslo, Norway;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway
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- Kure, E. H. (författare)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway;Univ South Eastern Norway, Fac Technol Nat Sci & Maritime Sci, Bo In Telemark, Norway
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- Pallisgaard, N. (författare)
- Zealand Univ Hosp, Dept Pathol, Roskilde, Denmark
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Spindler, K-L.G. (författare)
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(creator_code:org_t)
- Oxford University Press, 2019
- 2019
- Engelska.
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:7, s. 1088-1095
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Abstract
Ämnesord
Stäng
- Background 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 (1050-1645000) for B2M and 5959 alleles/ml (555-854167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6months for levels above ULN and 25.9months 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. Trial registration ClinicalTrials.gov, NCT00145314.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- colorectal cancer
- circulating cell-free DNA
- interleukin 6
- RAS
- BRAF
- prognostic biomarker
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Hamfjord, J.
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Guren, T. K.
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Dajani, O.
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Johansen, J. S.
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Glimelius, Bengt
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Sorbye, H.
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Pfeiffer, P.
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Lingjaerde, O. C ...
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Tveit, K. M.
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Kure, E. H.
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Pallisgaard, N.
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Spindler, K-L.G.
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