Extracellular water to total body water ratio may mediate the association between phase angle and mortality in patients with cancer cachexia: A single-center, retrospective study

Abstract

Background & aims: Recently, prognostic factors for cancer cachexia patients have been reported. We hypothesized that phase angle (PhA), which is measured by bioelectrical impedance analysis (BIA), might be a promising marker for assessing the nutritional status and prognosis of cancer patients. This study aimed to evaluate the predictive utility of PhA, which is mediated by several BIA factors and other anthropometric parameters, such as calf circumference, for the prognosis of cancer cachexia patients.

Methods: Consecutive patients (114, both outpatients and inpatients) with an unselected stage of cancer cachexia were recruited between July 2018 and December 2019 in Fujita Health University Hospital for this retrospective cohort study. Their mean age was 74.0 years (standard deviation, 8.5); among the total, 70 were men and 44 women. A time-dependent Cox proportional-hazards regression analysis (adjusted for age and sex) was performed to assess the following: 1) the association between potential mediators and mortality; 2) the association between five PhAs and statistically significant mediators from 1); and 3) the association between the five PhAs and mortality. Finally, Kaplan-Meier survival curves were constructed and compared between the two groups based on the patients' median baseline ratio of extracellular water (ECW) to total body water (TBW) using a log-rank test.

Results: The ECW/TBW ratio (hazard ratio [HR] per 1-interquartile range [IQR] increase: 2.87; 95% confidence interval [CI]: 1.46, 5.46; p < 0.001) and skeletal muscle mass index (HR per 1-IQR increase: 0.67; 95% CI: 0.51, 0.89; p = 0.001) were associated with mortality. All five PhAs were associated with the ECW/TBW ratio (p < 0.001). Before adjustment for the ECW/TBW ratio, all five PhAs were associated with mortality (p < 0.001); only the association of the PhAs of the left arm and the trunk retained the statistical significance after adjusting for confounders (p < 0.05). The median survival times in the low (370 days; 95% CI: 168, not calculated) and high ECW/TBW groups (101 days; 95% CI: 61, 219) differed significantly (p < 0.001).

Conclusions: The association between PhA and mortality in cancer cachexia patients was largely mediated by the ECW/TBW ratio. We believe that adjusting PhA for the ECW/TBW ratio may improve the prognostication of cancer patients with cachexia, ultimately improving their palliative care.

Keywords: (BIA); (ECW/TBW); (PhA); Bioelectrical impedance analysis; Cancer cachexia; Cancer prognostic predictor; Extracellular water to total body water ratio; Phase angle.