Advances in cancer treatment have increased childhood cancer patient's survival rates. However, many childhood cancer survivors (CCS) face long-term effects such as fatigue. This study assessed fatigue in CCS and healthy controls (HCs), its contributors, and associated outcomes. This cross-sectional study included 90 CCS and 55 age and sex-matched HCs. Fatigue was measured using the Pediatric Quality of Life Multidimensional Fatigue Scale, and modifiable contributors included sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and physical fitness (VO2 peak during a treadmill test). Quality of life (QoL) and emotional and cognitive functioning were evaluated using the Pediatric Quality of Life Inventory, Beck Depression Inventory II, Cognitive Failure Questionnaire, and the Impact of Event Scale-Revised. Stepwise linear regressions identified predictors of general, sleep/rest, cognitive, and total fatigue. General, cognitive, and total fatigue were significantly higher in CCS compared to HCs (44.7% vs. 23%, p < .001; cognitive: 64.7% vs. 29.3%, p < .001; total fatigue: 56.5% vs. 25%, p < .001). Sex, PSQI, PSQI × sex, and PSQI × VO₂ were significant predictors for general fatigue, PSQI and PSQI × VO₂ for cognitive fatigue, and PSQI for sleep/rest and total fatigue. Cognitive and total fatigue correlated most strongly with cognitive and work-related functioning, whereas general and sleep/rest fatigue were more related to psychosocial functioning. Fatigue is highly prevalent among CCS, with distinct factors influencing general, sleep/rest, cognitive, and total fatigue. Female survivors, those with poorer sleep quality and lower physical fitness, are at risk. This study underscores the need for tailored interventions for each type of fatigue. Improving sleep quality, physical fitness, and psychological well-being may contribute to reducing fatigue and enhancing overall quality of life in CCS.
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