Host phenotype is associated with reduced survival independent of tumour biology in patients with colorectal liver metastases

David P J van Dijk, Matthew Krill, Farshad Farshidfar, Ting Li, Sander S Rensen, Steven W M Olde Damink, Elijah Dixon, Francis R Sutherland, Chad G Ball, Vera C Mazurak, Vickie E Baracos, Oliver F Bathe, David P J van Dijk, Matthew Krill, Farshad Farshidfar, Ting Li, Sander S Rensen, Steven W M Olde Damink, Elijah Dixon, Francis R Sutherland, Chad G Ball, Vera C Mazurak, Vickie E Baracos, Oliver F Bathe

Abstract

Background: Most prognostic scoring systems for colorectal liver metastases (CRLMs) account for factors related to tumour biology. Little is known about the effects of the host phenotype to the tumour. Our objective was to delineate the relationship of systemic inflammation and body composition features [i.e. low skeletal muscle mass (sarcopenia) and low visceral adipose tissue (VAT)], two well-described host phenotypes in cancer.

Methods: Clinical data and pre-operative blood samples were collected from 99 patients who underwent resection of CRLM. Pre-operative computed tomography scans were available for 97 patients; body composition was analysed at the L3 level, stratified for sex and age. Clinicopathological variables, serum C-reactive protein (CRP), and various body composition variables were evaluated. Overall survival was evaluated as a function of these same variables in multivariate Cox regression analysis.

Results: Skeletal muscle was significantly correlated with VAT (r = 0.46, P < 0.001). Of patients with sarcopenia, 35 (65%) also had low VAT. C-reactive protein was elevated (≥5 mg/mL) in 42 patients (43.3%). Elevated CRP was more common in patients with sarcopenia (73.8% vs. 51.1%, P = 0.029). The most significant prognostic factors were the coincidence of elevated CRP and adverse body composition features (sarcopenia and/or low VAT; hazard ratio 4.3, 95% confidence interval 1.5-13.0, P = 0.008), as well as Fong clinical prognostic score (hazard ratio 2.9, 95% confidence interval 1.5-5.5, P = 0.002).

Conclusions: Body composition in patients with CRLM is not directly linked to the presence of systemic inflammation. However, when systemic inflammation coincides with sarcopenia and/or low VAT, prognosis is adversely affected, independent of the Fong clinical prognostic score.

Keywords: Colorectal cancer; Inflammation; Liver metastases; Sarcopenia.

Conflict of interest statement

All authors declare that they have no conflict of interest.

© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1
Figure 1
Sex‐specific values for body composition variables assessed by computed tomography scan. Boxes represent median and interquartile range. Whiskers are set at either the 25th or 75th percentile +1.5 times the interquartile range (Tukey method). Dots represent outliers. *P < 0.05. RA, radiation attenuation; SAT, subcutaneous adipose tissue; SM, skeletal muscle; VAT, visceral adipose tissue.
Figure 2
Figure 2
Relationships between serum markers and body composition. (A) Correlation matrix for serum markers and body composition. Spearman's correlation coefficients are represented in colour according to the heat map. Blank squares indicate non‐significant correlations (P > 0.05). (B) Venn diagram depicting the coexistence of systemic inflammation, sarcopenia, and low visceral adipose tissue in patients. CRP, C‐reactive protein; HMGB1, high mobility group box 1; RA, radiation attenuation; SAT, subcutaneous adipose tissue; SM, skeletal muscle; VAT, visceral adipose tissue.
Figure 3
Figure 3
Forest plot depicting the effect of clinical factors, body composition, and systemic inflammation on overall survival in patients with resectable colorectal liver metastases. Inflammation was defined as CRP ≥ 5 mg/L. Adverse body composition was defined as SM‐Z *P < 0.05. CRP, C‐reactive protein; RA, radiation attenuation; SAT, subcutaneous adipose tissue; SM, skeletal muscle; VAT, visceral adipose tissue.
Figure 4
Figure 4
Effect of combinations of risk factors on overall survival. (A) Flow diagram illustrating the derivation of phenotypes used for survival analysis. Four phenotypes were identified by categorizing the study population by systemic inflammation (CRP level ≥ 5 mg/L) and adverse body composition (low VAT and/or SM Z‐score). (B) Kaplan–Meier curve illustrating survival differences based on host risk factors. CRP, C‐reactive protein; SAT, subcutaneous adipose tissue; SM, skeletal muscle; VAT, visceral adipose tissue.

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