The association between low skeletal muscle mass and low skeletal muscle radiodensity with functional impairment, systemic inflammation, and reduced survival in patients with incurable cancer

Background and aims: Factors associated with the concomitant occurrence of low muscle mass and low muscle radiodensity are unclear. This study investigated whether different skeletal muscle phenotypes are associated with functional impairment, serum inflammatory markers, and survival in patients with incurable cancer.

Methods: Three hundred and twenty-six patients (median age, 60 years; 67.5% female) who had abdominal or pelvic computed tomography (CT) scans up to 30 days before the initial assessment were enrolled in the study. CT images were used for the assessment of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD). Optimal stratification analysis was used to derive cohort-specific cutoff points to define SMI and SMD groups with a higher risk for mortality (SMI, males <45.0 cm² /m² and females <44.0 cm² /m² ; SMD, males <34 Hounsfield units [HU] and females <30 HU). Based on these cutoffs, participants were classified into four phenotypes: low-risk SMI + low-risk SMD, high-risk SMI + low-risk SMD, low-risk SMI + high-risk SMD, and high-risk SMI + high-risk SMD.

Results: Phenotypes with high-risk SMI or high-risk SMD, especially when combined, were associated with low handgrip strength, poor performance status, higher C-reactive protein, and lower serum albumin levels. The phenotypes with high-risk SMD, regardless of low-risk SMI (hazard ratio [HR], 1.74; 95% CI, 1.05-2.88) or high-risk SMI (HR, 1.99; 95% CI, 1.29-3.05) were associated with higher 90 days' mortality risk.

Conclusion: In patients with incurable cancer, phenotype groups with high-risk SMI and high-risk SMD, particularly when combined, were associated with worse functional impairment and inflammation. Moreover, high-risk SMD was associated with increased mortality risk.