Guideline for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients: 2023 update.

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale.

Novel Adaption of the SARC-F Score to Classify Pediatric Hemato-Oncology Patients with Functional Sarcopenia.

Sarcopenia in pediatric hemato-oncology patients is undesirable because of the consequences it may have for treatment continuation and outcome, physical abilities and participation in daily life. An easy-to-use screening tool for sarcopenia will facilitate the identification of children at risk who need interventions to prevent serious physical deterioration. In the elderly, the use of the SARC-F score as a case-finding tool for sarcopenia is recommended. The aim of this cross-sectional study was to investigate the accuracy of the pediatric SARC-F (PED-SARC-F) for identifying sarcopenia in pediatric hemato-oncology patients, including the determination of a cut-off point for clinical use. Patients 3−20 years of age, under active treatment or within 12 months after treatment cessation were eligible. Patients had a physiotherapy assessment including a PED-SARC-F (0−10) and measurements of muscle strength (handheld dynamometry), physical performance (various tests) and/or muscle mass (bio-impedance analysis), as part of the standard of care. Spearman's correlation coefficient (rs) between the PED-SARC-F and physiotherapy outcomes were calculated. Structural sarcopenia was defined as low appendicular skeletal muscle mass (ASMM) in combination with low muscle strength and/or low physical performance. Functional sarcopenia indicated low muscle strength combined with low physical performance. Multiple logistic regression models were estimated to study the associations between the PED-SARC-F and structural/functional sarcopenia. To evaluate which cut-off point provides the most accurate classification, the area under the receiver operating characteristic curve (AUCs), sensitivity and specificity per point were calculated. In total, 215 assessments were included, 62% were performed in boys and the median age was 12.9 years (interquartile range: 8.5−15.8). The PED-SARC-F scores correlated moderately with the measurements of muscle strength (rs = −0.37 to −0.47, p < 0.001) and physical performance (rs = −0.45 to −0.66, p < 0.001), and weakly with ASMM (rs = −0.27, p < 0.001). The PED-SARC-F had an AUC of 0.90 (95% confidence interval (CI) = 0.84−0.95) for functional sarcopenia and 0.79 (95% CI = 0.68−0.90) for structural sarcopenia. A cut-off point of ≥5 had the highest specificity of 96% and a sensitivity of 74%. In conclusion, we adapted the SARC-F to a pediatric version, confirmed its excellent diagnostic accuracy for identifying functional sarcopenia and defined a clinically useful cut-off point in pediatric hemato-oncology patients.

The international Pediatric Oncology Exercise Guidelines (iPOEG).

Physical activity (PA) and exercise are safe and beneficial for children and adolescents affected by cancer. Yet, this population is not active enough to receive benefits. PA guideline and recommendation statements can support individual behavior and practice change. The purpose of this project was to develop the international Pediatric Oncology Exercise Guidelines (iPOEG), comprised of guideline and recommendation statements, to promote PA among children and adolescents affected by cancer. Guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to the iPOEG network (n = 9 core team members, n = 122 expert consensus committee members). Surveys included closed- and open-ended items informed by a literature synthesis and an in-person meeting. Responses were analyzed using descriptive statistics and content analysis. Consensus was defined as ≥ 80% agreement. Response rates to online surveys ranged from 82% to 91%. The iPOEG network agreed on four guideline and five recommendation statements, which highlight that movement is important for all children and adolescents affected by cancer. These statements are generic in nature as more research is still required to provide specific guidance on the frequency, intensity, time, and type of PA for this population. Nevertheless, the iPOEG statements represent available evidence and expert opinion, collectively suggesting that it is time for children and adolescents affected by cancer to move more.

Physical activity is safe and beneficial for children and adolescents affected by cancer. Yet, most are not active enough to receive benefits. Guideline and recommendation statements can help change individual behavior and practice. To develop such statements, guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to an international network (n = 131 experts). Surveys asked closed- and open-ended questions informed by a literature synthesis and an in-person meeting. Findings from the online surveys resulted in the international Pediatric Oncology Exercise Guidelines statements, which highlight that it is time for children and adolescents affected by cancer to move more.

Advancing the Field of Pediatric Exercise Oncology: Research and Innovation Needs.

The field of pediatric exercise oncology explores the relationships between physical activity (PA), including exercise, and a range of outcomes among children and adolescents affected by cancer. Although PA is safe and beneficial for this population, several important gaps in knowledge and practice remain. In this article, we describe research and innovation needs that were developed with a team of international experts and relevant literature, a series of online surveys, and an in-person meeting. Addressing these needs will contribute valuable knowledge and practice outputs to advance this field, ultimately enabling a greater number of children and adolescents affected by cancer to realize the benefits of moving more.

Management of fatigue in children and adolescents with cancer and in paediatric recipients of haemopoietic stem-cell transplants: a clinical practice guideline.

Fatigue is a prevalent and distressing symptom in children and adolescents with cancer and in those who have undergone haemopoietic stem-cell transplantation. A multidisciplinary and multinational group of experts in paediatric oncology and fatigue, together with patient advocates, developed a clinical practice guideline for management of fatigue on the basis of systematic reviews that included six paediatric and 456 adult randomised studies. We used the Grading of Recommendations Assessment, Development and Evaluation approach to generate recommendations, and made strong recommendations, supported by evidence of moderate quality, for use of physical activity, relaxation, and mindfulness to reduce fatigue. When these approaches are unsuccessful or not feasible, cognitive or cognitive behavioural therapies may be offered (weak recommendation supported by evidence of moderate quality). Maturity and cognitive ability of individual patients will affect the feasibility of interventions. Systemic pharmacological approaches should not be routinely used to manage fatigue in children. Apart from identification of optimal approaches to implement recommended interventions in clinical practice, future research should also address knowledge gaps, including establishment of minimum age thresholds for interventions and inclusion of paediatric patients in randomised trials of fatigue management.

Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

PURPOSE: Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. METHODS: We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. RESULTS: There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. CONCLUSIONS: Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority.

Mind and body practices for fatigue reduction in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.

PURPOSE: To determine whether non-physical activity mind and body practices reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients compared to control interventions. METHODS: We included randomized trials which compared non-physical activity mind and body practices compared with control interventions for the management of fatigue in cancer and HSCT patients. RESULTS: Among 55 trials (4975 patients), interventions were acupuncture or acupressure (n=12), mindfulness (n=11), relaxation techniques (n=10), massage (n=6), energy therapy (n=5), energizing yogic breathing (n=3) and others (n=8). When combined, all interventions significantly reduced fatigue severity compared to all controls (standardized mean difference -0.51, 95% confidence interval -0.73 to -0.29). More specifically, mindfulness and relaxation significantly reduced fatigue severity. CONCLUSIONS: Mindfulness and relaxation were effective at reducing fatigue severity in patients with cancer and HSCT recipients. Future studies should evaluate how to translate these findings into clinical practice across different patient groups.

Physical exercise training interventions for children and young adults during and after treatment for childhood cancer.

BACKGROUND: A decreased physical fitness has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of the disease and the treatment of childhood cancer. Exercise training for adult cancer patients has frequently been reported to improve physical fitness. In recent years, literature on this subject has also become available for children and young adults with cancer, both during and after treatment. This is an update of the original review that was performed in 2011. OBJECTIVES: To evaluate the effect of a physical exercise training intervention on the physical fitness (i.e. aerobic capacity, muscle strength, or functional performance) of children with cancer within the first five years from their diagnosis (performed either during or after cancer treatment), compared to a control group of children with cancer who did not receive an exercise intervention.To determine whether physical exercise within the first five years of diagnosis has an effect on fatigue, anxiety, depression, self efficacy, and HRQoL and to determine whether there are any adverse effects of the intervention. SEARCH METHODS: We searched the electronic databases of Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PEDro; ongoing trial registries and conference proceedings on 6 September 2011 and 11 November 2014. In addition, we performed a handsearch of reference lists. SELECTION CRITERIA: The review included randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias using standardized forms. Study quality was rated by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria. MAIN RESULTS: Apart from the five studies in the original review, this update included one additional RCT. In total, the analysis included 171 participants, all during treatment for childhood acute lymphoblastic leukaemia (ALL).The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention and intervention period varied in all the included studies. However, the control group always received usual care.All studies had methodological limitations, such as small numbers of participants, unclear randomization methods, and single-blind study designs in case of one RCT and all results were of moderate to very low quality (GRADE).Cardiorespiratory fitness was evaluated by the 9-minute run-walk test, timed up-and-down stairs test, the timed up-and-go time test, and the 20-m shuttle run test. Data of the 9-minute run-walk test and the timed up-and-down stairs test could be pooled. The combined 9-minute run-walk test results showed significant differences between the intervention and the control groups, in favour of the intervention group (standardized mean difference (SMD) 0.69; 95% confidence interval (CI) 0.02 to 1.35). Pooled data from the timed up-and-down stairs test showed no significant differences in cardiorespiratory fitness (SMD -0.54; 95% CI -1.77 to 0.70). However, there was considerable heterogeneity (I(2) = 84%) between the two studies on this outcome. The other two single-study outcomes, 20-m shuttle run test and the timed up-and-go test, also showed positive results for cardiorespiratory fitness in favour of the intervention group.Only one study assessed the effect of exercise on bone mineral density (total body), showing a statistically significant positive intervention effect (SMD 1.07; 95% CI 0.48 to 1.66). The pooled data on body mass index showed no statistically significant end-score difference between the intervention and control group (SMD 0.59; 95% CI -0.23 to 1.41).Three studies assessed flexibility. Two studies assessed ankle dorsiflexion. One study assessed active ankle dorsiflexion, while the other assessed passive ankle dorsiflexion. There were no statistically significant differences between the intervention and control group with the active ankle dorsiflexion test; however, in favour of the intervention group, they were found for passive ankle dorsiflexion (SMD 0.69; 95% CI 0.12 to 1.25). The third study assessed body flexibility using the sit-and-reach distance test, but identified no statistically significant difference between the intervention and control group.Three studies assessed muscle strength (knee, ankle, back and leg, and inspiratory muscle strength). Only the back and leg strength combination score showed statistically significant differences on the muscle strength end-score between the intervention and control group (SMD 1.41; 95% CI 0.71 to 2.11).Apart from one sub-scale of the cancer scale (Worries; P value = 0.03), none of the health-related quality of life scales showed a significant difference between both study groups on the end-score. For the other outcomes of fatigue, level of daily activity, and adverse events (all assessed in one study), there were no statistically significant differences between the intervention and control group.None of the included studies evaluated activity energy expenditure, time spent on exercise, anxiety and depression, or self efficacy as an outcome. AUTHORS' CONCLUSIONS: The effects of physical exercise training interventions for childhood cancer participants are not yet convincing. Possible reasons are the small numbers of participants and insufficient study designs, but it can also be that this type of intervention is not as effective as in adult cancer patients. However, the first results show some positive effects on physical fitness in the intervention group compared to the control group. There were positive intervention effects for body composition, flexibility, cardiorespiratory fitness, muscle strength, and health-related quality of life (cancer-related items). These were measured by some assessment methods, but not all. However, the quality of the evidence was low and these positive effects were not found for the other assessed outcomes, such as fatigue, level of daily activity, and adverse events. There is a need for more studies with comparable aims and interventions, using a higher number of participants that also include diagnoses other than ALL.

Validity of the Pediatric Running-Based Anaerobic Sprint Test to Determine Anaerobic Performance in Healthy Children.

PURPOSE: To determine criterion validity of the pediatric running-based anaerobic sprint test (RAST) as a nonsophisticated field test for evaluating anaerobic performance in healthy children and adolescents. METHODS: Data from 65 healthy children (28 boys and 37 girls between 6 and 18 years of age, mean ± SD age: 10.0 ± 2.8 years) who completed both the pediatric RAST and the 30-s Wingate anaerobic test (WAnT) on a cycle ergometer in a randomized order were analyzed. Peak power (PP) and mean power (MP) were the primary outcome measures for both tests. RESULTS: There were no significant sex-differences in PP and MP attained at the pediatric RAST and the WAnT. Age was strongly correlated to pediatric RAST and WAnT performance (Spearman's rho values ranging from 0.85 to 0.90, with p < .001 for all coefficients). We found high correlation coefficients between pediatric RAST performance and WAnT performance for both PP (Spearman's rho: 0.86; p < .001) and MP (Spearman's rho: 0.91; p < .001). CONCLUSION: The pediatric RAST can be used as a valid and nonsophisticated field test for the assessment of anaerobic performance in healthy children and adolescents. For clinical evaluative purposes, we suggest to use MP of the pediatric RAST when assessing glycolytic power in the absence of the WAnT.

Physical exercise training interventions for children and young adults during and after treatment for childhood cancer.

BACKGROUND: A decreased physical fitness and impaired social functioning has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of disease and treatment of childhood cancer and by behavioural and social elements. Exercise training for adults during or after cancer therapy has frequently been reported to improve physical fitness and social functioning. More recently, literature on this subject became available for children and young adults with cancer, both during and after treatment. OBJECTIVES: This review aimed to evaluate the effect of a physical exercise training intervention (at home, at a physical therapy centre, or hospital based) on the physical fitness of children with cancer, in comparison with the physical fitness in a care as usual control group. The intervention needed to be offered within the first five years from diagnosis.The second aim was to assess the effects of a physical exercise training intervention in this population on fatigue, anxiety, depression, self efficacy, and health-related quality of life and to assess the adverse effects of the intervention. SEARCH METHODS: For this review the electronic databases of CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, and ongoing trial registries were searched on 6 September 2011. In addition, a handsearch of reference lists and conference proceedings was performed in that same month. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer. DATA COLLECTION AND ANALYSIS: By the use of standardised forms two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias. Quality of the studies was rated by using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria. MAIN RESULTS: Five articles were included in this review: four RCTs (14, 14, 28, and 51 participants) and one CCT (24 participants). In total 131 participants (74 boys, 54 girls, three unknown) were included in the analysis, all being treated for childhood acute lymphoblastic leukaemia (ALL). The study interventions were all implemented during chemotherapy treatment.The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention, as well as the intervention period, which ranged from 10 weeks to two years, varied in all the included studies. In all included studies the control group received care as usual.All studies had methodological limitations, such as small numbers of participants, unclear randomisation methods, and single-blind study designs in case of an RCT.Cardiorespiratory fitness was studied by the use of the nine-minute run-walk test, the timed up-and-down stairs test, and the 20-m shuttle run test. Only the up-and-down stairs test showed significant differences between the intervention and the control group, in favour of the intervention group (P value = 0.05, no further information available).Bone mineral density was assessed in one study, in which a statistically significant difference in favour of the exercise group was identified (standardised mean difference (SMD) 1.07; 95% confidence interval (CI) 0.48 to 1.66; P value < 0.001). Body mass index was assessed in two studies. The pooled data on this item did not show a statistically significant difference between the intervention and control study group.Flexibility was assessed in three studies. In one study the active ankle dorsiflexion method was used to assess flexibility and the second study they used the passive ankle dorsiflexion test. No statistically significant difference between the intervention and control group was identified with the active ankle dorsiflexion test, whereas with the passive test method a statistically significant difference in favour of the exercise group was found (SMD 0.69; 95% CI 0.12 to 1.25; P value = 0.02). The third study assessed body flexibility by the use of the sit-and-reach distance test; no statistically significant difference between the intervention and control group was identified.One study assessed the effects of an inspiratory muscle training programme aimed to train the lung muscles and increase physical fitness. This study reported no significant effect on either inspiratory or expiratory muscle strength. Two other studies using either knee and ankle strength changes by hand-held dynamometry or the number of completed push-ups (with knees on the ground) and a peripheral quantitative computed tomography of the tibia to determine the muscle mass did not identify statistically significant differences in muscle strength/endurance.The level of daily activity, health-related quality of life, fatigue, and adverse events were assessed in one study only; for all these items no statistically significant differences between the intervention and control group were found.None of the included studies evaluated the outcomes activity energy expenditure, time spent exercising, anxiety and depression, or self efficacy. AUTHORS' CONCLUSIONS: The effects of physical exercise training interventions for childhood cancer participants are not yet convincing due to small numbers of participants and insufficient study methodology. Despite that, first results show a trend towards an improved physical fitness in the intervention group compared to the control group. Changes in physical fitness were seen by improved body composition, flexibility, and cardiorespiratory fitness. However, the evidence is limited and these positive effects were not found for the other assessed outcomes, such as muscle strength/endurance, the level of daily activity, health-related quality of life, and fatigue. There is a need for more studies with comparable aims and interventions, using higher numbers of participants and for studies with another childhood cancer population than ALL only.

Development, feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors.

OBJECTIVE: The aim of this study was to develop a 12-week exercise training program (comprising aerobic and strength exercises), and to study the feasibility and efficacy of this exercise program in children who survived acute lymphoblastic leukemia. SAMPLE AND METHODS: A 12-week exercise program was developed and tested for feasibility in nine children who survived cancer. RESULTS: From the 16 eligible children for the intervention, 9 participated, while 4 were able to complete the entire program. Feasibility of the program was scored by five children, two of them reported the program as being too demanding. The participating physiotherapists were satisfied with training methodology and training progress. The efficacy of the program on muscle strength, exercise capacity, functional mobility and fatigue showed no significant differences between pre and post training. CONCLUSION: In designing a community-based exercise training program, not only the stage of the disease needs to be considered, but more so the age of the children, the variety of exercises, the location of implementation and even more importantly the views and motivation of the parents concerning the execution of an exercise training program. A careful balance between these parameters could lead to a greater adherence and by that, to a better outcome of these programs.

Motor performance and functional ability in preschool- and early school-aged children with Juvenile Idiopathic Arthritis: a cross-sectional study.

OBJECTIVE: To describe the level of motor performance and functional skills in young children with JIA. METHODS: In a cross-sectional study in 56 preschool-aged (PSA) and early school- aged children (ESA) with JIA according to ILAR classification, motor performance was measured with the Bayley Scales of Infant Development II (BSID2) and the Movement Assessment Battery for Children (M-ABC). Functional skills were measured with the Pediatric Evaluation of Disability Inventory (PEDI). Disease outcome was measured with a joint count on swelling/range of joint motion, functional ability and joint pain. RESULTS: Twenty two PSA children (mean age 2.1 years) with a mean Developmental Index of the BSID2 of 77.9 indicating a delayed motor performance; 45% of PSA children showed a severe delayed motor performance. Mean PEDI scores were normal, 38% of PSA scored below -2 SD in one or more domains of the PEDI. Thirty four ESA children (mean age 5.2 years) with a mean M-ABC 42.7, indicating a normal motor performance, 12% of ESA children had an abnormal score. Mean PEDI scores showed impaired mobility skills, 70% of ESA children scored below -2 SD in one or more domains of the PEDI. Disease outcome in both age groups demonstrated low to moderate scores. Significant correlations were found between age at disease onset, disease duration and BSID2 or M-ABC and between disease outcome and PEDI in both age cohorts. CONCLUSION: More PSA children have more impaired motor performance than impaired functional skills, while ESA children have more impairment in functional skills. Disease onset and disease duration are correlated with motor performance in both groups. Impaired motor performance and delayed functional skills is primarily found in children with a polyarticular disease course. Clinical follow up and rehabilitation programs should also focus on motor performance and functional skills development in young children with JIA.