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

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

doi:10.1371/journal.pone.0087746

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

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

11 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	e87746
Tidsskrift	PLOS ONE
Vol/bind	9
Udgave nummer	2
Sider (fra-til)	1-8
Antal sider	8
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0087746
Status	Udgivet - 3 feb. 2014

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10.1371/journal.pone.0087746

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Tarpgaard, L. S., Guren, T. K., Glimelius, B., Christensen, I. J., Pfeiffer, P., Kure, E. H., Sorbye, H., Ikdahl, T., Yilmaz, M., Johansen, J. S., & Tveit, K. M. (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. PLOS ONE, 9(2), 1-8. [e87746]. https://doi.org/10.1371/journal.pone.0087746

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. / Tarpgaard, Line S; Guren, Tormod K; Glimelius, Bengt et al.

I: PLOS ONE, Bind 9, Nr. 2, e87746, 03.02.2014, s. 1-8.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Tarpgaard, LS, Guren, TK, Glimelius, B, Christensen, IJ, Pfeiffer, P, Kure, EH, Sorbye, H, Ikdahl, T, Yilmaz, M, Johansen, JS & Tveit, KM 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', PLOS ONE, bind 9, nr. 2, e87746, s. 1-8. https://doi.org/10.1371/journal.pone.0087746

@article{9f7cb4b5f9944907849e9d5bac34a77d,

title = "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",

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.",

keywords = "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",

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

year = "2014",

month = feb,

day = "3",

doi = "10.1371/journal.pone.0087746",

language = "English",

volume = "9",

pages = "1--8",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "2",

}

TY - JOUR

T1 - Plasma YKL-40 in Patients with Metastatic Colorectal Cancer Treated with First Line Oxaliplatin-Based Regimen with or without Cetuximab

T2 - RESULTS from the NORDIC VII Study

AU - Tarpgaard, Line S

AU - Guren, Tormod K

AU - Glimelius, Bengt

AU - Christensen, Ib J

AU - Pfeiffer, Per

AU - Kure, Elin H

AU - Sorbye, Halfdan

AU - Ikdahl, Tone

AU - Yilmaz, Mette

AU - Johansen, Julia S

AU - Tveit, Kjell Magne

PY - 2014/2/3

Y1 - 2014/2/3

N2 - 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.

AB - 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.

KW - Adipokines

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal, Humanized

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Case-Control Studies

KW - Colorectal Neoplasms

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Fluorouracil

KW - Follow-Up Studies

KW - Humans

KW - Lectins

KW - Leucovorin

KW - Male

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Neoplasm Staging

KW - Organoplatinum Compounds

KW - Prognosis

KW - Survival Rate

KW - Tumor Markers, Biological

KW - Young Adult

U2 - 10.1371/journal.pone.0087746

DO - 10.1371/journal.pone.0087746

M3 - Journal article

C2 - 24498368

SN - 1932-6203

VL - 9

SP - 1

EP - 8

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 2

M1 - e87746

ER -

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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