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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

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Line S Tarpgaard, Tormod K Guren, Bengt Glimelius, Ib J Christensen, Per Pfeiffer, Elin H Kure, Halfdan Sorbye, Tone Ikdahl, Mette Yilmaz, Julia S Johansen, Kjell Magne Tveit

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.

Original languageEnglish
Article numbere87746
JournalPloS one
Issue number2
Pages (from-to)1-8
Number of pages8
StatePublished - 2014

    Research areas

  • Adipokines, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Case-Control Studies, Colorectal Neoplasms, Enzyme-Linked Immunosorbent Assay, Female, Fluorouracil, Follow-Up Studies, Humans, Lectins, Leucovorin, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Organoplatinum Compounds, Prognosis, Survival Rate, Tumor Markers, Biological, Young Adult

ID: 137673043