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PLoS One. 2014 Feb 3;9(2):e87746. doi: 10.1371/journal.pone.0087746. eCollection 2014.

Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study.

Author information

1
Department of Oncology, Odense University Hospital, Odense, Denmark and University of Southern Denmark, Odense, Denmark.
2
Department of Oncology, Oslo University Hospital, Oslo, Norway.
3
Departments of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden and Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
4
The Finsen Laboratory, Copenhagen University Hospital, Copenhagen, Denmark and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
5
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
6
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
7
Department of Oncology, Aalborg Hospital, Aalborg, Denmark.
8
Departments of Oncology and Medicine, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

Erratum in

  • PLoS One. 2014;9(5):e98836.

Abstract

BACKGROUND:

We aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with first-line oxaliplatin and 5-flourouracil with or without cetuximab.

PATIENTS AND METHODS:

A total of 566 patients in the NORDIC VII Study were randomized 1∶1∶1 to arm A (Nordic FLOX), arm B (Nordic FLOX + cetuximab), or arm C (Nordic FLOX + cetuximab for 16 weeks followed by cetuximab alone as maintenance therapy). Pretreatment plasma samples were available from 510 patients. Plasma YKL-40 was determined by ELISA and dichotomized according to the age-corrected 95% YKL-40 level in 3130 healthy subjects.

RESULTS:

Pretreatment plasma YKL-40 was elevated in 204 patients (40%), and median YKL-40 was higher in patients with mCRC than in healthy subjects (age adjusted, P<0.001). Patients with elevated YKL-40 had shorter PFS than patients with normal YKL-40 (7.5 vs. 8.2 months; hazard ratio (HR)  = 1.27 95% confidence interval (CI) 1.05-1.53 P = 0.013) and shorter OS (16.8 vs. 23.9 months; HR = 1.33, 1.04-1.69, P = 0.024). Multivariate Cox analysis demonstrated that elevated pretreatment YKL-40 was an independent biomarker of short OS (HR = 1.12, 1.01-1.25, P = 0.033). The ratio of the updated plasma YKL-40 (i.e. level after 1, 2, 8 weeks of treatment, and at end of treatment compared to the baseline level) was associated with OS (HR = 1.27, 1.06-1.52, P = 0.011).

CONCLUSIONS:

Plasma YKL-40 is an independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy alone or combined with cetuximab.

PMID:
24498368
PMCID:
PMC3912025
DOI:
10.1371/journal.pone.0087746
[Indexed for MEDLINE]
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