TY - JOUR
T1 - The Prognostic Value of Pre-Treatment Circulating Biomarkers of Systemic Inflammation (CRP, dNLR, YKL-40, and IL-6) in Vulnerable Older Patients with Metastatic Colorectal Cancer Receiving Palliative Chemotherapy
T2 - The Randomized NORDIC9-Study
AU - Liposits, Gabor
AU - Skuladottir, Halla
AU - Ryg, Jesper
AU - Winther, Stine Brændegaard
AU - Möller, Sören
AU - Hofsli, Eva
AU - Shah, Carl Henrik
AU - Poulsen, Laurids Østergaard
AU - Berglund, Åke
AU - Qvortrup, Camilla
AU - Osterlund, Pia
AU - Johansen, Julia S.
AU - Glimelius, Bengt
AU - Sorbye, Halfdan
AU - Pfeiffer, Per
N1 - Funding Information:
This investigator-initiated study was partly funded by: Taiho Pharmaceuticals, Nordic Group; The Danish Cancer Society (grant number: R269-A15859); Academy of Geriatric Cancer Research (AgeCare); The Swedish Cancer Society; Region of Southern Denmark.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - Appropriate patient selection for palliative chemotherapy is crucial in patients with metastatic colorectal cancer (mCRC). We investigated the prognostic value of C-reactive protein (CRP), derived neutrophil-to-lymphocyte ratio (dNLR), Interleukin (IL)-6, and YKL-40 on progression-free survival (PFS) and overall survival (OS) in the NORDIC9 cohort. The randomized NORDIC9-study included patients ≥70 years with mCRC not candidates for standard full-dose combination chemotherapy. Participants received either full-dose S1 (Teysuno) or a dose-reduced S1 plus oxaliplatin. Blood samples were collected at baseline and biomarkers were dichotomized according to standard cut-offs. Multivariable analyses adjusted for age, sex, ECOG performance status, and treatment allocation; furthermore, C-statistics were estimated. In total, 160 patients with a median age of 78 years (IQR: 76–81) were included between 2015 and 2017. All investigated biomarkers were significantly elevated in patients with either weight loss, ≥3 metastatic sites, or primary tumor in situ. In multivariable analyses, all markers showed significant association with OS; the highest HR was observed for CRP (HR = 3.40, 95%CI: 2.20–5.26, p < 0.001). Regarding PFS, statistically significant differences were found for CRP and IL-6, but not for dNLR and YKL-40. Applying C-statistics, CRP indicated a good prognostic model for OS (AUC = 0.72, 95%CI: 0.67–0.76). CRP is an easily available biomarker, which may support therapeutic decision-making in vulnerable older patients with mCRC.
AB - Appropriate patient selection for palliative chemotherapy is crucial in patients with metastatic colorectal cancer (mCRC). We investigated the prognostic value of C-reactive protein (CRP), derived neutrophil-to-lymphocyte ratio (dNLR), Interleukin (IL)-6, and YKL-40 on progression-free survival (PFS) and overall survival (OS) in the NORDIC9 cohort. The randomized NORDIC9-study included patients ≥70 years with mCRC not candidates for standard full-dose combination chemotherapy. Participants received either full-dose S1 (Teysuno) or a dose-reduced S1 plus oxaliplatin. Blood samples were collected at baseline and biomarkers were dichotomized according to standard cut-offs. Multivariable analyses adjusted for age, sex, ECOG performance status, and treatment allocation; furthermore, C-statistics were estimated. In total, 160 patients with a median age of 78 years (IQR: 76–81) were included between 2015 and 2017. All investigated biomarkers were significantly elevated in patients with either weight loss, ≥3 metastatic sites, or primary tumor in situ. In multivariable analyses, all markers showed significant association with OS; the highest HR was observed for CRP (HR = 3.40, 95%CI: 2.20–5.26, p < 0.001). Regarding PFS, statistically significant differences were found for CRP and IL-6, but not for dNLR and YKL-40. Applying C-statistics, CRP indicated a good prognostic model for OS (AUC = 0.72, 95%CI: 0.67–0.76). CRP is an easily available biomarker, which may support therapeutic decision-making in vulnerable older patients with mCRC.
KW - biomarker
KW - C-reactive protein
KW - chemotherapy
KW - colorectal cancer
KW - frailty
KW - Interleukin-6
KW - neutrophil-to-lymphocyte ratio
KW - older patients
KW - survival
KW - YKL-40
U2 - 10.3390/jcm11195603
DO - 10.3390/jcm11195603
M3 - Article
AN - SCOPUS:85139741972
VL - 11
IS - 19
M1 - 5603
ER -
