Associations Between Physical Fitness and Fatigue in Adolescent Childhood Cancer Survivors: The PACCS Study

Fatigue is a prevalent and distressing late effect among childhood cancer survivors (CCSs), yet its physiological determinants remain unclear. This study examined the associations between physical fitness (VO₂peak and muscular strength), physical function (sit-to-stand [STS] performance), physical activity, and fatigue in adolescent CCSs, and whether these associations differ from those observed in healthy controls.

This cross-sectional analysis was part of the international multicenter Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study, including CCSs and age- and sex-matched healthy controls. Fatigue was assessed using the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale. Physical fitness and function were evaluated by cardiopulmonary exercise testing (VO₂peak), isometric muscular strength (knee extension, chest press, and handgrip), and the 1-min STS test. Physical activity was measured by accelerometry. Associations between physical fitness, physical activity, and fatigue were examined using multivariable mixed-effects linear regression models.

A total of 123 CCSs (mean age 13.5 ± 2.5 years, 6.7 ± 3.5 years posttreatment) and 99 controls (mean age 13.1 ± 2.6 years) were included. Total fatigue scores among CCSs and controls were 72.6 ± 17.1 and 74.8 ± 15.7, respectively (p = 0.324). Higher VO₂peak (β = 0.66, 95% confidence interval [CI] 0.14-1.17, p = 0.012) and greater muscular strength (β = 5.85, 95% CI 0.63-11.08, p = 0.028) were associated with less fatigue in CCSs, whereas activity levels were not associated with fatigue. No significant differences were observed in the association of physical fitness or physical activity measures with fatigue between CCSs and controls.

Higher physical fitness, but not physical activity level, was associated with lower fatigue in adolescent CCSs, with similar associations observed in healthy controls. These findings highlight physical fitness as a potential target for fatigue management in adolescent CCSs.