Metabolomic Associations With Fatigue and Physical Function in Children With Cancer: A Pilot Study

Background: Fatigue is a frequently reported symptom in children undergoing cancer treatment. Prior research shows an inverse relationship between fatigue and physical activity. Less is known about fatigue's relationship with physical function or the underlying biological mechanisms of fatigue. This study explored associations among fatigue, physical function, and associated metabolites. Methods: Children (7-18 years) provided serum samples and self-reports of fatigue and lower extremity physical function (mobility) using Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) surveys at two timepoints during cancer therapy. PROMIS scores were categorized as high/low per established cut points (high fatigue T >47.5; high physical function T >51.5). High-resolution liquid chromatography-mass spectrometry extracted 29 metabolites hypothesized a priori to be associated with fatigue or physical function. Descriptive statistics summarized PROMIS scores, and linear mixed effect models estimated metabolite associations adjusting for age, gender and steroid use. Results: Forty children participated (female, 53%; 7-12 years, 38%; 13-18 years 62%; Hodgkins Lymphoma, 33%; Acute Lymphoblastic/Lymphocytic Leukemia, 40%; Osteosarcoma, 10%; Other, 17%). Physical function and fatigue were inversely related: T1 (r = -0.64; p < .001) and T2 (r = -0.63; p < .001). One metabolite (indole-3-latic acid) differentiated between low and high fatigue. Five metabolites differentiated significantly between low and high physical function (4-Hydroxybenzoic acid, m-Coumaric acid, myoinositol, tryptophan, and tyrosine). Conclusions:These findings substantiate prior studies showing metabolites, particularly amino acids, significantly associated with fatigue and physical function. All significant metabolites were associated with the gut microbiome. Physical function was inversely corelated with fatigue providing another potential intervention for fatigue management.