Background: Children with cancer experience fatigue related to cancer and its treatment. Fatigue can be debilitating and distressing, resulting in poor health-related quality of life. The prevalence of fatigue reported in literature among children with cancer is variable, and it is uncertain which children with cancer are at increased risk of experiencing fatigue during their cancer treatment. Despite being a common symptom, there is a limited understanding of current practices of screening and management of fatigue among pediatric oncology patients.

Hypothesis: We hypothesized that fatigue will be prevalent among children with cancer during cancer treatment, and various patient-, disease- and treatment-related factors will influence the prevalence of fatigue during treatment. We also hypothesized that pediatric hematology oncology healthcare professionals (HCPs) will have limited knowledge about the screening and management of fatigue, along with underutilization of fatigue management guidelines in North America.

Objectives: The aims of my thesis were to (1) determine the prevalence of fatigue among children undergoing cancer treatment; (2) identify the factors associated with fatigue among children undergoing cancer treatment; (3) understand the knowledge of pediatric hematology oncology HCPs about fatigue; (4) explore the perspectives of HCPs on screening and management of fatigue;(5) identify barriers to the screening and management of fatigue, and; (6) understand HCPs perspectives regarding future clinical trials on fatigue in pediatric oncology.

Methods: We conducted a systematic review and meta-analysis of observational studies to determine the prevalence of, and factors associated with, fatigue among children during cancer treatment. Systematic searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and SCOPUS were conducted from inception to May 22, 2023, to identify relevant citations. Pooled prevalence estimates were calculated using an inverse variance, random-effects model. We used the Joanna Briggs critical appraisal checklist to assess study quality. To accomplish objectives (3-6), we conducted a web-based American cross-sectional survey of pediatric hematologist oncologists, nurses and nurse practitioners utilizing evidence-based survey methods. We used descriptive statistics to summarize the quantitative data. We used univariable and multivariable logistic regression analyses to assess the HCPs- and treatment center-related factors associated with fatigue knowledge, screening, and management strategies. Framework analysis was used to analyze the open-ended responses to the survey questions.

Results: We included 47 studies in our systematic review; 26 contributed to the prevalence outcome, whereas 29 contributed to the secondary outcome of factors associated with fatigue. Substantial heterogeneity in the patient characteristics, cancer diagnoses, treatment modalities, fatigue assessment tools, study designs and sample size was observed. The pooled prevalence of fatigue among 2699 children undergoing cancer treatment was 73% (95% CI,66%-79%; I2 96%). Considerable heterogeneity was observed in the patient-, disease- and treatment-related factors associated with fatigue in the included studies. In our survey of 528 pediatric hematology oncology HCPs, 35% of the HCPs attended fatigue educational events in the previous five years. Only 32% of the HCPs reported fatigue screening in their centers during outpatient visits; 91% of fatigue screening was reported to be conducted verbally without utilizing a validated fatigue screening tool. Most HCPs responded that assessing patients for fatigue during cancer treatment is very important. Although 18% of HCPs reported being familiar with fatigue management guidelines, only 1% reported that these guidelines were implemented at their oncology centers. Common themes believed to improve fatigue screening and management included enhancing the education of HCPs and patients, routine fatigue screening throughout the cancer continuum, and developing and implementing fatigue assessment tools, guidelines, interventions and resources for treating fatigue. The barriers to fatigue screening and management included a lack of education, routine screening and fatigue screening tools. Most HCPs (94%) considered clinical trials for fatigue management necessary and favoured clinical trials of non-pharmacological interventions compared to pharmacological interventions.

Conclusions: The prevalence of fatigue among children with cancer during treatment is variable but high. Several factors have been heterogeneously reported to be associated with fatigue. Most North American pediatric hematology-oncology HCPs consider it essential to address fatigue among children with cancer. The utilization of fatigue screening tools and implementation of fatigue management guidelines is low in routine clinical practice. Future studies should address the implementation of fatigue screening tools and fatigue management pathways in clinical practice. Clinical trials are required to determine the efficacy of developmentally appropriate non-pharmacological interventions for fatigue management in this population.