Evaluation of physical function and its association with body composition, quality of life and biomarkers in cancer cachexia patients

Abstract

There are currently no approved treatments for cancer cachexia. One of the main barriers to developing a treatment for this indication is the lack of consensus on clinically important tools for assessing functional impairment in this setting. This issue is of critical importance because functional improvement is likely to be required for approval by regulatory agencies. This cross-sectional study aimed to evaluate various functional performance measures and establish their association with body composition, energy expenditure, biomarkers, and patient-reported quality of life (QOL). Physical function, body composition, energy expenditure, cytokines, testosterone, and patient-reported QOL were compared between men with solid tumors with cachexia (CAC; N=48), without cachexia (CNC; N=48), and weight-stable patients without cancer (CON; N=37). Receiver Operator Characteristic curves and multivariate regression were performed to identify functional impairment cut-points and predictors of physical function, respectively. Patients with CAC displayed lower total lean and appendicular lean mass, stair climb power (SCP), upper body strength, and bioavailable testosterone, and displayed higher energy expenditure than CNC or CON (p≤0.03); CAC showed lower handgrip, respiratory quotient, and appetite, and higher cytokines and fatigue than CON (p≤0.032). A cut-point of 336 Watts for SCP provided 78% sensitivity and 77% specificity for classification of CAC (p=0.001); SCP also performed better than other measures tested when compared to CON-derived normatives. Upper body strength exhibited moderate sensitivity and specificity for classification of CAC (p≤0.02). Elevated relative energy expenditure and cytokines negatively predicted, and muscle mass positively predicted, various muscle strength outcomes. Stair climb power and upper body strength may have potential as discriminatory tests for functional impairment in patients with cancer cachexia.