Mogens K Boisen1, Christine V Madsen, Christian Dehlendorff, Anders Jakobsen, Julia S Johansen, Karina D Steffensen. 1. *Department of Oncology, University of Copenhagen Herlev Hospital, Herlev; †Department of Oncology, Vejle Hospital, Vejle; ‡Danish Cancer Society, Danish Cancer Society Research Center, Copenhagen; §Department of Medicine, University of Copenhagen Herlev Hospital, Herlev; and ∥Faculty of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Abstract
OBJECTIVE: YKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patients with ovarian cancer treated with bevacizumab. METHODS: One hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during treatment. Both raw YKL-40 concentrations and age-corrected percentiles of normal YKL-40 level were used. Associations between plasma YKL-40 level and progression-free survival (PFS) and overall survival were tested using univariate and multivariate Cox proportional hazards models. RESULTS: Baseline plasma YKL-40 levels were higher in patients with poor performance status, less differentiated tumors, residual disease after primary surgery, higher than the median serum CA-125 level, and higher than the median serum vascular endothelial growth factor level. Age-corrected percentile of normal plasma YKL-40 greater than the lowest quartile (Q1, 85th percentile) was associated with shorter PFS in univariate (hazard ratio, 1.83; 95% confidence interval, 1.15-2.89; P = 0.010) and multivariate analyses and shorter overall survival in univariate analysis (hazard ratio, 1.96; 95% confidence interval, 1.27-3.03; P = 0.003). Increase in plasma YKL-40 during bevacizumab treatment, with correction for baseline plasma YKL-40, was a predictor of shorter PFS. Using normal versus elevated plasma YKL-40 as a cutoff did not provide the same discriminative value. CONCLUSIONS: Low plasma YKL-40 at baseline and during treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab.
OBJECTIVE:YKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patients with ovarian cancer treated with bevacizumab. METHODS: One hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during treatment. Both raw YKL-40 concentrations and age-corrected percentiles of normal YKL-40 level were used. Associations between plasma YKL-40 level and progression-free survival (PFS) and overall survival were tested using univariate and multivariate Cox proportional hazards models. RESULTS: Baseline plasma YKL-40 levels were higher in patients with poor performance status, less differentiated tumors, residual disease after primary surgery, higher than the median serum CA-125 level, and higher than the median serum vascular endothelial growth factor level. Age-corrected percentile of normal plasma YKL-40 greater than the lowest quartile (Q1, 85th percentile) was associated with shorter PFS in univariate (hazard ratio, 1.83; 95% confidence interval, 1.15-2.89; P = 0.010) and multivariate analyses and shorter overall survival in univariate analysis (hazard ratio, 1.96; 95% confidence interval, 1.27-3.03; P = 0.003). Increase in plasma YKL-40 during bevacizumab treatment, with correction for baseline plasma YKL-40, was a predictor of shorter PFS. Using normal versus elevated plasma YKL-40 as a cutoff did not provide the same discriminative value. CONCLUSIONS: Low plasma YKL-40 at baseline and during treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab.
Authors: Ankush Chandra; Arman Jahangiri; William Chen; Alan T Nguyen; Garima Yagnik; Matheus P Pereira; Saket Jain; Joseph H Garcia; Sumedh S Shah; Harsh Wadhwa; Rushikesh S Joshi; Jacob Weiss; Kayla J Wolf; Jung-Ming G Lin; Sören Müller; Jonathan W Rick; Aaron A Diaz; Luke A Gilbert; Sanjay Kumar; Manish K Aghi Journal: Cancer Res Date: 2020-02-10 Impact factor: 12.701
Authors: Malgorzata Fuksiewicz; Beata Kotowicz; Andrzej Rutkowski; Joanna Achinger-Kawecka; Michal Wagrodzki; Maria M Kowalska Journal: Technol Cancer Res Treat Date: 2018-01-01