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.
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.


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.
Department of Oncology, Odense University Hospital, Odense, Denmark and University of Southern Denmark, Odense, Denmark.
Line S
LS
Tarpgaard
Department of Oncology, Oslo University Hospital, Oslo, Norway.
Tormod K
TK
Guren
Departments of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden and Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
Bengt
B
Glimelius
The Finsen Laboratory, Copenhagen University Hospital, Copenhagen, Denmark and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
Ib J
IJ
Christensen
Department of Oncology, Odense University Hospital, Odense, Denmark and University of Southern Denmark, Odense, Denmark.
Per
P
Pfeiffer
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Elin H
EH
Kure
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Halfdan
H
Sorbye
Department of Oncology, Oslo University Hospital, Oslo, Norway.
Tone
T
Ikdahl
Department of Oncology, Aalborg Hospital, Aalborg, Denmark.
Mette
M
Yilmaz
Departments of Oncology and Medicine, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
Julia S
JS
Johansen
Department of Oncology, Oslo University Hospital, Oslo, Norway.
Kjell Magne
KM
Tveit
D054392:Adipokines / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D000068818:Cetuximab; D000071451:Chitinase-3-Like Protein 1; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D037102:Lectins / Q000097:blood*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
D054392:Adipokines; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil