IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results From CALGB (Alliance)/SWOG 80405.

MedStar author(s):
Citation: JNCI Cancer Spectrum. 5(1), 2021 02.JNCI Cancer Spectrum. 5(1):pkaa074, 2021 Feb.PMID: 33426464Institution: MedStar Washington Hospital CenterDepartment: Hematology/OncologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Adiponectin/bl [Blood] | *Colorectal Neoplasms/bl [Blood] | *Colorectal Neoplasms/mo [Mortality] | *Insulin-Like Growth Factor Binding Protein 3/bl [Blood] | *Insulin-Like Growth Factor Binding Proteins/bl [Blood] | *Insulin-Like Growth Factor I/an [Analysis] | Aged | C-Peptide/bl [Blood] | Colorectal Neoplasms/ge [Genetics] | Confidence Intervals | Female | Humans | Male | Middle Aged | Neoplasm Proteins/bl [Blood] | Progression-Free Survival | Proportional Hazards Models | Prospective StudiesYear: 2021ISSN:
  • 2515-5091
Name of journal: JNCI cancer spectrumAbstract: Background: Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study.Conclusions: Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation. Copyright (c) The Author(s) 2020. Published by Oxford University Press.Methods: Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute-sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided.Results: Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; P nonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; P trend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; P trend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; P trend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (P nonlinearity = .03).All authors: Atkins JN, Benson AB 3rd, Blanke CD, Brown JC, Fuchs CS, Goldberg RM, Guercio BJ, Innocenti F, Lenz HJ, Mayer RJ, Meyerhardt JA, Mullen BC, Niedzwiecki D, Nixon AB, O'Neil BH, O'Reilly EM, Ou FS, Polite BN, Pollak MN, Shaw JE, Venook AP, Zhang SOriginally published: JNCI Cancer Spectrum. 5(1):pkaa074, 2021 Feb.Fiscal year: FY2021Digital Object Identifier: Date added to catalog: 2021-02-17
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Journal Article MedStar Authors Catalog Article 33426464 Available 33426464

Background: Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study.

Conclusions: Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation. Copyright (c) The Author(s) 2020. Published by Oxford University Press.

Methods: Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute-sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided.

Results: Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; P nonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; P trend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; P trend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; P trend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (P nonlinearity = .03).

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