Johansen SH; Faculty of Medicine, University of Oslo, Oslo, Norway.
Edvardsen E; Raastad T; Ruud E;et al

Pediatric Blood & Cancer. 73(9):e70478, 2026 Sep.

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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 (beta = 0.66,
95% confidence interval [CI] 0.14-1.17, p = 0.012) and greater muscular
strength (beta = 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.

CONCLUSION: 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.