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Dietary and Exercise Interventions for Pediatric Oncology Patients: The Way Forward

Dietary and Exercise Interventions for Pediatric Oncology Patients: The Way Forward Abstract This review focuses on diet and exercise interventions that have been conducted in pediatric cancer and pediatric stem cell transplant patients. It examines the different reasons for conducting lifestyle interventions with attention to the different outcome measurements and feasibility of these measures with an argument toward a need for standardization to move the field forward. Pediatric cancer now has a 5-year survival rate of more than 80%. Thus, there is a growing number of long-term survivors at risk for therapy-related complications. These include obesity and predisposition to the metabolic syndrome in those exposed to cranial radiation and steroids (1,2). Many pediatric cancer patients are deconditioned at diagnosis; fitness and loss of lean body mass often worsen on therapy and persist into long-term follow-up (3–5). Additionally, malnutrition and/or obesity from disease, treatment exposure, and illness-related poor eating habits potentially impact chances of oncologic cure (6). Finally, the pediatric cancer experience can cause psychological strain, negatively impacting health-related quality of life (HRQOL) (3). Fortunately, these disease- and therapy-related conditions are potentially responsive to diet and exercise interventions. Attempts to find unifying best practices for lifestyle interventions in childhood cancer patients are hampered by lack of large randomized data, diversity of outcomes, and heterogeneous treatment strategies, making it difficult to draw solid conclusions (7–11). This review describes existing interventions and outcome measures for pediatric oncology patients, with special attention intervention feasibility as it relates to setting and timing, and provides suggestions for future trials. Dietary Interventions in Pediatric Cancer Modifying nutritional intake has benefits for everyone including maximizing chances of disease cure, preventing infection, and managing body composition before it perpetuates as obesity during survivorship. Unfortunately, surveys indicate that nutritional services are inconsistent across pediatric oncology centers; not all patients get assistance in maintaining a healthy diet (12,13) Recent evidence suggests that being overweight during treatment for acute lymphoblastic leukemia increases risk of persistent disease and relapse (6,14), which really requires a paradigm shift for nutrition management during therapy. Because children typically lose weight during initial intense phases of treatment, the focus has traditionally been on optimizing calories. However, 36% of children are overweight when diagnosed with acute lymphoblastic leukemia, and 79% consume more than recommended total calories (1,15). Maintenance of normal body mass index (BMI) and weight gain are accompanied by gains in body fat percentage, often with corresponding loss in lean mass (sarcopenic obesity) (16) due to the toxicity of specific treatment modalities and compounded by inactivity. In fact, emerging evidence indicates that caloric intake actually decreases in the most common pediatric cancer populations (acute lymphoblastic leukemia [ALL] and central nervous system tumors) during therapy but fat intake increases, thus a focus on the quality of nutritional intake should be prioritized over total calories (1,17,18). Nutritional interventions during therapy have yielded only modest results, most have been limited to children with ALL, and none have evaluated the impact of the intervention on survival. One study implemented a nutritional counseling program in 22 pediatric ALL patients during maintenance chemotherapy (12 in intervention group) over a year, with a resultant decrease in caloric intake but no changes in body weight or waist circumference (19). Another trial used a phone counseling intervention promoting healthy eating and physical activity, targeting caregivers of pediatric cancer patients (n = 53; 27 in intervention group) (20). Modest reductions in caloric intake among caregivers and in sugary beverage consumption among children were reported. Both caregivers and children had modest reductions in BMI. Two other randomized studies that added nutritional education to physical activity interventions, one during maintenance chemotherapy for ALL (21) and one after completion of ALL therapy (22), had no impact on weight, even in the presence of increased physical activity. Patients with obesity caused by tumors involving the hypothalamus often struggle to lose weight despite dietary interventions. One comprehensive clinic demonstrates that weight gain can be mitigated by a multidisciplinary approach focused on social skills classes, cognitive behavior therapy, and motivational interviewing (23). Barriers to Successful Nutrition Interventions There are several barriers that prevent successful implementation of nutritional interventions. First, although there are many national recommendations for healthy eating, there are no standard programs for recommended nutritional intake during cancer therapy. As a result, it is challenging to set benchmarks for ideal intake and to know which components of dietary intake should be targeted during treatment (12). Secondly, most dietary intake interventions to date have focused on the patient only (10). Because a patient’s dietary intake is often dependent on what their family is eating, patients might not have the opportunity to make healthy choices if they are not available in the family’s meal and/or snack repertoire. Thus, family-based approaches are the most likely to result in successful change and/or choice. Finally, dietary intake varies greatly between individuals, with reasons for suboptimal (too little, too much, the wrong foods) dietary intake dependent on age, preference, religion, altered taste related to chemotherapy administration, nausea, and parent’s desire to provide something for their sick child. Interventions will have to incorporate individualized nutrition plans in the context of reproduceable and evaluable nutritional guidelines. Specific Nutritional Modifications Prescribing a neutropenic diet (avoiding raw vegetables and fresh deli meats), conceived to prevent infections in pediatric oncology patients by limiting introduction of bacteria into the gastrointestinal tract (24), is not uncommon in practice (25), even though data from a randomized study (n = 150) indicate that there is no difference in infection rates in patients using a neutropenic diet compared to those who followed Food and Drug Administration food safety guidelines (24). Furthermore, emerging evidence indicates that bacteria in the microbiome may actually help prevent infections. There is little data to support other diet modifications during therapy other than a case series indicating feasibility of a high-fat, low-carbohydrate diet, often used to treat refractory seizures, in pediatric brain tumor patients (26). A summary of key nutritional recommendations for the way forward is given in Table 1. Table 1. Key recommendations for dietary intake studies Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Open in new tab Table 1. Key recommendations for dietary intake studies Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Open in new tab Barriers to Successful Exercise Interventions Exercise is good for everyone including children with cancer, given their increased risk of premature cardiovascular disease and mortality (27). However, there are some barriers that make exercise difficult. A pediatric cancer diagnosis is a major life event. Appropriate focus on cure stresses families and leads to complications such as unemployment, divorce, and home relocation, all which make it difficult to incorporate exercise into a daily routine (28). Although parents often recognize that their children are overweight, most do not remember that their oncologist discussed potential complications of being overweight (29). Other barriers reported by patients and families include being too tired, too busy, afraid of injury, and lack of access to exercise resources and having negative thoughts and feelings about themselves (30). Exercise trials remove some of these barriers (access, fear of injury) but are difficult to conduct in families disrupted and consumed by the intensity of cancer therapy (30,31). Another potential barrier to exercise is asking the patient to be active when their family is not. As with nutritional interventions, physical activity interventions are most likely to be successful when the entire family is included. Designing a feasible and successful intervention is challenging and requires input from family stakeholders in terms of when to intervene, where to intervene (venue), and what an acceptable time commitment would be. Exercise Interventions Targeting Body Composition Weight loss is a common aim in exercise interventions. However, in 12 studies, no statistically significant weight loss occurred in the intervention group, and in 6 randomized trials delivered during active ALL therapy, weight gain occurred regardless of group assignment (21,22,32–41), In addition, inclusion criteria, intervention timing, and measurement techniques are not uniform. Positive findings include one study among patients whose BMI was above the 85th percentile, where rate of BMI gain (height and weight measurements) during therapy was less in those in the exercise group than in the control group (22), another that demonstrated loss of fat mass (dual x-ray absorptiometry measurement) during the first 2 years after therapy among children with ALL who were randomly assigned to exercise during therapy when compared to control subjects (35), and one that showed statistically significant decreases in overall and abdominal body fat (skinfold and waist circumference measurements) in 17 ALL survivors after a 16-week exercise intervention (36). Further study is needed to establish inclusion criteria (targeting those at greatest risk), to identify the most appropriate timing for intervention, and to determine the best body mass assessment tool. Exercise Interventions Targeting Physical Deconditioning Physical deconditioning in children with cancer includes loss of strength, flexibility, fitness, and mobility, all which result from or contribute to inactivity. Evaluating the effects of interventions on these outcomes is challenging, because studies (n = 36; 30 in cancer, 6 in stem cell transplant [SCT]) are small (mean = 28, subjects range = 6–97) and use heterogeneous measurement tools and outcome assessment timing (21,22,32–65). In addition, adherence to different exercise interventions varies from 25% to 100%, making it difficult to determine if null results are associated with poor adherence or the result of inadequate exercise dose. Adherence was highest in studies where the exercise was directly observed by study personnel, or when conducted in an inpatient setting as opposed to in-home settings. Nevertheless, home or community-based interventions are necessary, because it is difficult to translate labor-intensive and costly supervised or hospital-based programs into most clinical settings. Increasing physical activity is a focus for many exercise interventions. Sedentary and active behavior can be measured objectively using accelerometers, now incorporated into most smart phones. Accelerometer data are hard to evaluate. Complete data require full time wear, and children frequently forget to wear them, or lose them. Nevertheless, they do provide objective data. Self-report or exercise logs are also used to evaluate activity but provide less reliable estimates (37,53,65) or have low adherence (46,65), respectively. Of 11 studies that used accelerometers, 10 showed no statistically significant change in moderate-to-vigorous activity for the intervention group when compared to control subjects (21,22,32,34,48–50,52,53,57,63). Although these data are discouraging, sensor technology is improving. Newer devices (66) that stick to the body and have prolonged durability, or data captured on smart phones typically carried everywhere, may be a better way to capture movement-derived data. Other goals of exercise interventions are to improve flexibility, strength, and motor function. Ankle range of motion, a common problem for children with ALL, has been evaluated with goniometry in 10 studies, with 3 showing some improvement in the intervention group (32,51,61), 1 showing worsening (35), and the rest showing no significant change (32,33,35,38–40,46,51,61,64). General flexibility was assessed in three studies (one improvement) using the sit-and-reach test (21,33,64,67). Handheld dynamometers or ability to lift increasing weight loads are used to measure strength. Knee extension (six studies used, three showing improvement); hip abduction (three studies, one improvement); handgrip (six studies, three improvement); shoulder flexion (two studies, no change) (32,33,40–42,46,50,51,56); and increases in weight load (four studies, three improvement) (34,38,39,54) have been measured. The Bruininks-Oseretsky Test of Motor Proficiency was used to test motor function in three studies. Statistically Significant improvement in response to exercise was reported in two (33,55,57). Psychometric assessment to determine an optimal set of tests to evaluate flexibility, strength, and motor function in children with cancer would improve interpretability of studies. Fitness and functional mobility are also exercise intervention targets. Fitness assessment by evaluating peak oxygen uptake on cycle ergometers (four studies, one showing improvement) or treadmills (two studies, both showing improvement) is the gold standard but is time intensive and may be difficult for children who are deconditioned (32,38–40,55,68). Walk tests—distance walked in a predetermined number of minutes—are also used to assess fitness (eight studies, six improvement) (33,41,42,51,53,59,60,62). Walk tests require an open hallway clear of obstacles, are effort dependent, and again may be difficult for deconditioned children. Functional mobility is evaluated with the Timed Up and Go Test—the time to stand from a chair, walk 10 feet and return to sitting (seven studies, three improvement) (34,38–41,60,64), or the Timed Up and Down Stairs—the time required to ascend and descend one flight of a standard staircase (seven studies, two improvement) (34,38–41,51,60). Like the walk tests, these measures of functional mobility are easy to perform but are effort dependent and require a motivated child. Exercise Interventions Targeting HRQOL HRQOL is also a target of pediatric oncology exercise interventions (69,70). The most commonly used measure to date is the 23-item Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale (69). It was designed for ages 2–18 years and uses both child reporting and parent proxy to assess physical, emotional, social, and school functioning. Fourteen exercise intervention (five randomized) studies in children with cancer have used this measure. These vary by sample size (6–69 participants), type of exercise (11 traditional, 3 yoga), encompass all phases of treatment (newly diagnosed, long-term survivorship), use of proxies, and frequency of reporting (time between assessments 3 weeks–18 months) (32,37,43,45–47,50,51,54,59,60,64,71). Seven studies showed improvement in at least 1 domain. In one study, the exercise intervention was delivered early in leukemia therapy. HRQOL decreased as therapy became more intense (47). In another study, authors found no difference in HRQOL between exercise and control groups as they progressed further out from end of therapy (32), illustrating the difficulty of evaluating effects of exercise interventions on HRQOL, an outcome largely influenced by cancer treatment intensity. Two other common patient and/or proxy reported outcome measures are the 27-item PedsQL 3.0 Cancer Module (69), which assesses pain and/or injury, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication, and the 18-item Multidimensional Fatigue Inventory, which assesses general, sleep and/or rest, and cognitive fatigue. Just one of four exercise intervention studies in children with cancer demonstrated improvement on the PedsQL 3.0 Cancer Module or the Multidimensional Fatigue Inventory as a result of the intervention, and gains were likely not clinically signficant (32,34,37,54,56,59,60,65,71). Many other measures have been employed. In all cases, these measurements have been evaluated to be feasible, but standardization is needed across trials for these measurements to be comparable. Exercise Interventions Targeting Other Cancer Comorbidities Exercise has other potential benefits that could prevent or mitigate complications of pediatric cancer therapy, including immune system dysfunction, cardiac toxicity, and neural recovery, and bone mineral density. Data are preliminary, but somewhat positive. Five studies with 6–10 patients in the exercise group resulted in an association between exercise and a boost in neutrophil count among children with cancer (72–74), a small increase in natural killer cell cytotoxicity by boosting CD56dim cells, and mitigation of fall in dendritic cell counts among children after stem cell transplantation (75,76). Among survivors exposed to anthracyclines, Smith et al. (77) demonstrated that exercise is safe among those with reduced ejection fraction. Studies also indicate that that exercise can improve endothelial structures and function and peak circumferential systolic and diastolic strain (68,78,79). Among pediatric brain tumor survivors, exercise is associated with increasing brain white matter, hippocampal volume, and cortical thickness (80,81). Studies evaluating the effects of exercise on bone mineral density and metabolic function in children with cancer and among survivors are largely null with small sample sizes and poor intervention adherence (82–84). One randomized study, using low-magnitude mechanical stimulation as an exercise mimetic, did have a statistically and clinically meaningful (0.5 standard deviations) effect on bone mineral density in children and adolescents with low bone mineral density after completion of cancer therapy (85). There is a need for more studies with larger sample sizes of the effects of exercise on immune function, cardiovascular health, neural recovery, bone density, and metabolic health in pediatric oncology patients. A summary of key exercise recommendations for the way forward is given in Table 2. Table 2. Key recommendations for exercise intervention studies Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Open in new tab Table 2. Key recommendations for exercise intervention studies Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Open in new tab Diet and exercise interventions are feasible in the pediatric oncology and SCT populations, however, there are many study design issues and barriers to participation that need to be overcome. There are many compelling reasons for conducting these interventions, and when designing new interventions, consideration should be made to pick outcomes that are reliable and reproducible. Standardization of outcome measures is needed so that studies can be compared and combined. Notes Affiliations of authors: Vanderbilt-Ingram Cancer Center, Nashville, TN (AJE); Monroe Carell Jr. Children’s Hospital at Vanderbilt Division of Pediatric Hematology-Oncology, Nashville, TN (AJE); Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN (KKN). The authors have no conflicts of interest to report. References 1 Esbenshade AJ , Simmons JH , Koyama T , et al. . Body mass index and blood pressure changes over the course of treatment of pediatric acute lymphoblastic leukemia . Pediatr Blood Cancer . 2011 ; 56 3 : 372 – 378 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Esbenshade AJ , Simmons JH , Koyama T , et al. . Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy . Pediatr Blood Cancer . 2013 ; 60 8 : 1287 – 1291 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Deisenroth A , Sontgerath R , Schuster AJ , et al. . Muscle strength and quality of life in patients with childhood cancer at early phase of primary treatment . Pediatr Hematol Oncol . 2016 ; 33 6 : 393 – 407 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Ness KK , DeLany JP , Kaste SC , et al. . Energy balance and fitness in adult survivors of childhood acute lymphoblastic leukemia . Blood . 2015 ; 125 22 : 3411 – 3419 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Ness KK , Kaste SC , Zhu L , et al. . Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia . Leuk Lymphoma . 2015 ; 56 4 : 1004 – 1011 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Orgel E , Tucci J , Alhushki W , et al. . Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia . Blood . 2014 ; 124 26 : 3932 – 3938 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Braam KI , van der Torre P , Takken T , et al. . Physical exercise training interventions for children and young adults during and after treatment for childhood cancer . Cochrane Database Syst Rev . 2016 ; 3 : CD008796. Google Scholar PubMed WorldCat 8 Morales JS , Valenzuela PL , Rincon-Castanedo C , et al. . Exercise training in childhood cancer: a systematic review and meta-analysis of randomized controlled trials . Cancer Treat Rev . 2018 ; 70 : 154 – 167 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Oberoi S , Robinson PD , Cataudella D , et al. . Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: a systematic review and meta-analysis of randomized trials . Crit Rev Oncol Hematol . 2018 ; 122 : 52 – 59 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Raber M , Swartz MC , Santa Maria D , et al. . Parental involvement in exercise and diet interventions for childhood cancer survivors: a systematic review . Pediatr Res . 2016 ; 80 3 : 338 – 346 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Wang KW , Chau R , Fleming A , et al. . The effectiveness of interventions to treat hypothalamic obesity in survivors of childhood brain tumours: a systematic review . Obes Rev . 2017 ; 18 8 : 899 – 914 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Ladas EJ , Sacks N , Brophy P , et al. . Standards of nutritional care in pediatric oncology: results from a nationwide survey on the standards of practice in pediatric oncology. A Children’s Oncology Group study . Pediatr Blood Cancer . 2006 ; 46 3 : 339 – 344 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Selwood K , Ward E , Gibson F. Assessment and management of nutritional challenges in children’s cancer care: a survey of current practice in the United Kingdom . Eur J Oncol Nurs . 2010 ; 14 5 : 439 – 446 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Orgel E , Genkinger JM , Aggarwal D , et al. . Association of body mass index and survival in pediatric leukemia: a meta-analysis . Am J Clin Nutr . 2016 ; 103 3 : 808 – 817 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Ladas EJ , Orjuela M , Stevenson K , et al. . Dietary intake and childhood leukemia: the Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) cohort study . Nutrition . 2016 ; 32 10 : 1103 – 1109 e1 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Orgel E , Mueske NM , Sposto R , et al. . Limitations of body mass index to assess body composition due to sarcopenic obesity during leukemia therapy . Leuk Lymphoma . 2018 ; 59 1 : 138 – 145 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Ladas EJ , Orjuela M , Stevenson K , et al. . Fluctuations in dietary intake during treatment for childhood leukemia: a report from the DALLT cohort . [published online ahead of print March 1, 2019]. Clin Nutr . 2019 . doi:10.1016/j.clnu.2018.12.021. WorldCat 18 Bakish J , Hargrave D , Tariq N , et al. . Evaluation of dietetic intervention in children with medulloblastoma or supratentorial primitive neuroectodermal tumors . Cancer . 2003 ; 98 5 : 1014 – 1020 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Li R , Donnella H , Knouse P , et al. . A randomized nutrition counseling intervention in pediatric leukemia patients receiving steroids results in reduced caloric intake . Pediatr Blood Cancer . 2017 ; 64 2 : 374 – 380 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Stern M , Bleck J , Ewing LJ , et al. . NOURISH-T: targeting caregivers to improve health behaviors in pediatric cancer survivors with obesity . Pediatr Blood Cancer . 2018 ; 65 5 : e26941. Google Scholar Crossref Search ADS PubMed WorldCat 21 Moyer-Mileur LJ , Ransdell L , Bruggers CS. Fitness of children with standard-risk acute lymphoblastic leukemia during maintenance therapy: response to a home-based exercise and nutrition program . J Pediatr Hematol Oncol . 2009 ; 31 4 : 259 – 266 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Huang JS , Dillon L , Terrones L , et al. . Fit4Life: a weight loss intervention for children who have survived childhood leukemia . Pediatr Blood Cancer . 2014 ; 61 5 : 894 – 900 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Rakhshani N , Jeffery AS , Schulte F , et al. . Evaluation of a comprehensive care clinic model for children with brain tumor and risk for hypothalamic obesity . Obesity (Silver Spring) . 2010 ; 18 9 : 1768 – 74 . Google Scholar Crossref Search ADS PubMed WorldCat 24 Moody KM , Baker RA , Santizo RO , et al. . A randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patients . Pediatr Blood Cancer . 2018 ; 65 1 : e26711. Google Scholar Crossref Search ADS WorldCat 25 Braun LE , Chen H , Frangoul H. Significant inconsistency among pediatric oncologists in the use of the neutropenic diet . Pediatr Blood Cancer . 2014 ; 61 10 : 1806 – 1810 . Google Scholar Crossref Search ADS PubMed WorldCat 26 Nebeling LC , Miraldi F , Shurin SB , et al. . Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports . J Am Coll Nutr . 1995 ; 14 2 : 202 – 208 . Google Scholar Crossref Search ADS PubMed WorldCat 27 Scott JM , Li N , Liu Q , et al. . Association of exercise with mortality in adult survivors of childhood cancer . JAMA Oncol . 2018 ; 4 10 : 1352 – 1358 . Google Scholar Crossref Search ADS PubMed WorldCat 28 Lau S , Lu X , Balsamo L , et al. . Family life events in the first year of acute lymphoblastic leukemia therapy: a children’s oncology group report . Pediatr Blood Cancer . 2014 ; 61 12 : 2277 – 2284 . Google Scholar Crossref Search ADS PubMed WorldCat 29 Jones GL , McClellan W , Raman S , et al. . Parental perceptions of obesity and obesity risk associated with childhood acute lymphoblastic leukemia . J Pediatr Hematol Oncol . 2017 ; 39 5 : 370 – 375 . Google Scholar Crossref Search ADS PubMed WorldCat 30 Ross WL , Le A , Zheng DJ , et al. . Physical activity barriers, preferences, and beliefs in childhood cancer patients . Support Care Cancer . 2018 ; 26 7 : 2177 – 2184 . Google Scholar Crossref Search ADS PubMed WorldCat 31 van Dijk-Lokkart EM , Braam KI , Huisman J , et al. . Factors influencing childhood cancer patients to participate in a combined physical and psychosocial intervention program: quality of life in motion . Psychooncology . 2015 ; 24 4 : 465 – 471 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Braam KI , van Dijk-Lokkart EM , Kaspers GJL , et al. . Effects of a combined physical and psychosocial training for children with cancer: a randomized controlled trial . BMC Cancer . 2018 ; 18 1 : 1289. Google Scholar Crossref Search ADS PubMed WorldCat 33 Esbenshade AJ , Friedman DL , Smith WA , et al. . Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia . Pediatr Phys Ther . 2014 ; 26 3 : 301 – 307 . Google Scholar Crossref Search ADS PubMed WorldCat 34 Fiuza-Luces C , Padilla JR , Soares-Miranda L , et al. . Exercise intervention in pediatric patients with solid tumors: the physical activity in pediatric cancer trial . Med Sci Sports Exerc . 2017 ; 49 2 : 223 – 230 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Hartman A , Te Winkel ML , van Beek RD , et al. . A randomized trial investigating an exercise program to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukemia . Pediatr Blood Cancer . 2009 ; 53 1 : 64 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Jarvela LS , Kemppainen J , Niinikoski H , et al. . Effects of a home-based exercise program on metabolic risk factors and fitness in long-term survivors of childhood acute lymphoblastic leukemia . Pediatr Blood Cancer . 2012 ; 59 1 : 155 – 160 . Google Scholar Crossref Search ADS PubMed WorldCat 37 Keats MR , Culos-Reed SN. A community-based physical activity program for adolescents with cancer (project TREK): program feasibility and preliminary findings . J Pediatr Hematol Oncol . 2008 ; 30 4 : 272 – 280 . Google Scholar Crossref Search ADS PubMed WorldCat 38 San Juan AF , Chamorro-Vina C , Moral S , et al. . Benefits of intrahospital exercise training after pediatric bone marrow transplantation . Int J Sports Med . 2008 ; 29 5 : 439 – 446 . Google Scholar Crossref Search ADS PubMed WorldCat 39 San Juan AF , Fleck SJ , Chamorro VC , et al. . Effects of an intrahospital exercise program intervention for children with leukemia . Med Sci Sports Exerc . 2007 ; 39 1 : 13 – 21 . Google Scholar Crossref Search ADS PubMed WorldCat 40 Takken T , van der Torre P , Zwerink M , et al. . Development, feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors . Psychooncology . 2009 ; 18 4 : 440 – 448 . Google Scholar Crossref Search ADS PubMed WorldCat 41 Yildiz Kabak V , Duger T , Uckan Cetinkaya D. Investigation of the effects of an exercise program on physical functions and activities of daily life in pediatric hematopoietic stem cell transplantation . Pediatr Blood Cancer . 2016 ; 63 9 : 1643 – 1648 . Google Scholar Crossref Search ADS PubMed WorldCat 42 Bogg TF , Broderick C , Shaw P , et al. . Feasibility of an inpatient exercise intervention for children undergoing hematopoietic stem cell transplant . Pediatr Transplantation . 2015 ; 19 8 : 925 – 931 . Google Scholar Crossref Search ADS WorldCat 43 Chung OK , Li HC , Chiu SY , et al. . Sustainability of an integrated adventure-based training and health education program to enhance quality of life among Chinese childhood cancer survivors: a randomized controlled trial . Cancer Nurs . 2015 ; 38 5 : 366 – 374 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Diorio C , Celis Ekstrand A , Hesser T , et al. . Development of an individualized yoga intervention to address fatigue in hospitalized children undergoing intensive chemotherapy . Integr Cancer Ther . 2016 ; 15 3 : 279 – 284 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Geyer R , Lyons A , Amazeen L , et al. . Feasibility study: the effect of therapeutic yoga on quality of life in children hospitalized with cancer . Pediatr Phys Ther . 2011 ; 23 4 : 375 – 379 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Gilliam MB , Ross K , Futch L , et al. . A pilot study evaluation of a web-based token economy to increase adherence with a community-based exercise intervention in child and adolescent cancer survivors . Rehabil Oncol . 2011 ; 29 2 : 16 – 22 . Google Scholar Crossref Search ADS WorldCat 47 Gohar SF , Comito M , Price J , et al. . Feasibility and parent satisfaction of a physical therapy intervention program for children with acute lymphoblastic leukemia in the first 6 months of medical treatment . Pediatr Blood Cancer . 2011 ; 56 5 : 799 – 804 . Google Scholar Crossref Search ADS PubMed WorldCat 48 Hinds PS , Hockenberry M , Rai SN , et al. . Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer . J Pain Symptom Manage . 2007 ; 33 6 : 686 – 697 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Hooke MC , Gilchrist L , Tanner L , et al. . Use of a fitness tracker to promote physical activity in children with acute lymphoblastic leukemia . Pediatr Blood Cancer . 2016 ; 63 4 : 684 – 689 . Google Scholar Crossref Search ADS PubMed WorldCat 50 Howell CR , Krull KR , Partin RE , et al. . Randomized web-based physical activity intervention in adolescent survivors of childhood cancer . Pediatr Blood Cancer . 2018 ; 65 8 : e27216. Google Scholar Crossref Search ADS PubMed WorldCat 51 Marchese VG , Chiarello LA , Lange BJ. Effects of physical therapy intervention for children with acute lymphoblastic leukemia . Pediatr Blood Cancer . 2004 ; 42 2 : 127 – 133 . Google Scholar Crossref Search ADS PubMed WorldCat 52 Mendoza JA , Baker KS , Moreno MA , et al. . A Fitbit and Facebook mHealth intervention for promoting physical activity among adolescent and young adult childhood cancer survivors: a pilot study . Pediatr Blood Cancer . 2017 ; 64 12 : e26660 . Google Scholar Crossref Search ADS WorldCat 53 Ovans JA , Hooke MC , Bendel AE , et al. . Physical therapist coaching to improve physical activity in children with brain tumors: a pilot study . Pediatr Phys Ther . 2018 ; 30 4 : 310 – 317 . Google Scholar Crossref Search ADS PubMed WorldCat 54 Perondi MB , Gualano B , Artioli GG , et al. . Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia . J Sports Sci Med . 2012 ; 11 3 : 387 – 392 . Google Scholar PubMed WorldCat 55 Piscione PJ , Bouffet E , Timmons B , et al. . Exercise training improves physical function and fitness in long-term paediatric brain tumour survivors treated with cranial irradiation . Eur J Cancer . 2017 ; 80 : 63 – 72 . Google Scholar Crossref Search ADS PubMed WorldCat 56 Rosenhagen A , Bernhorster M , Vogt L , et al. . Implementation of structured physical activity in the pediatric stem cell transplantation . Klin Padiatr . 2011 ; 223 3 : 147 – 151 . Google Scholar Crossref Search ADS PubMed WorldCat 57 Sabel M , Sjolund A , Broeren J , et al. . Active video gaming improves body coordination in survivors of childhood brain tumours . Disabil Rehabil . 2016 ; 38 21 : 2073 – 2084 . Google Scholar Crossref Search ADS PubMed WorldCat 58 Speyer E , Herbinet A , Vuillemin A , et al. . Effect of adapted physical activity sessions in the hospital on health-related quality of life for children with cancer: a cross-over randomized trial . Pediatr Blood Cancer . 2010 ; 55 6 : 1160 – 1166 . Google Scholar Crossref Search ADS PubMed WorldCat 59 Su HL , Wu LM , Chiou SS , et al. . Assessment of the effects of walking as an exercise intervention for children and adolescents with cancer: a feasibility study . Eur J Oncol Nurs . 2018 ; 37 : 29 – 34 . Google Scholar Crossref Search ADS PubMed WorldCat 60 Tanir MK , Kuguoglu S. Impact of exercise on lower activity levels in children with acute lymphoblastic leukemia: a randomized controlled trial from Turkey . Rehabil Nurs . 2013 ; 38 1 : 48 – 59 . Google Scholar Crossref Search ADS PubMed WorldCat 61 Tanner L , Sencer S , Hooke MC. The stoplight program: a proactive physical therapy intervention for children with acute lymphoblastic leukemia . J Pediatr Oncol Nurs . 2017 ; 34 5 : 347 – 357 . Google Scholar Crossref Search ADS PubMed WorldCat 62 Wallek S , Senn-Malashonak A , Vogt L , et al. . Impact of the initial fitness level on the effects of a structured exercise therapy during pediatric stem cell transplantation . Pediatr Blood Cancer . 2018 ; 65 2 : e26851 . Google Scholar Crossref Search ADS WorldCat 63 Winter CC , Muller C , Hardes J , et al. . The effect of individualized exercise interventions during treatment in pediatric patients with a malignant bone tumor . Support Care Cancer . 2013 ; 21 6 : 1629 – 1636 . Google Scholar Crossref Search ADS PubMed WorldCat 64 Wurz A , Chamorro-Vina C , Guilcher GM , et al. . The feasibility and benefits of a 12-week yoga intervention for pediatric cancer out-patients . Pediatr Blood Cancer . 2014 ; 61 10 : 1828 – 1834 . Google Scholar Crossref Search ADS PubMed WorldCat 65 Yeh CH , Man Wai JP , Lin US , et al. . A pilot study to examine the feasibility and effects of a home-based aerobic program on reducing fatigue in children with acute lymphoblastic leukemia . Cancer Nurs . 2011 ; 34 1 : 3 – 12 . Google Scholar Crossref Search ADS PubMed WorldCat 66 Levine DM , Ouchi K , Blanchfield B , et al. . Hospital-level care at home for acutely Ill adults: a pilot randomized controlled trial . J Gen Intern Med . 2018 ; 33 5 : 729 – 736 . Google Scholar Crossref Search ADS PubMed WorldCat 67 Huang TT , Ness KK. Exercise interventions in children with cancer: a review . Int J Pediatr . 2011 ; 2011 : 461512. Google Scholar Crossref Search ADS PubMed WorldCat 68 Jarvela LS , Saraste M , Niinikoski H , et al. . Home-based exercise training improves left ventricle diastolic function in survivors of childhood ALL: a tissue doppler and velocity vector imaging study . Pediatr Blood Cancer . 2016 ; 63 9 : 1629 – 1635 . Google Scholar Crossref Search ADS PubMed WorldCat 69 Varni JW , Burwinkle TM , Katz ER , et al. . The PedsQL in pediatric cancer: reliability and validity of the pediatric quality of life inventory generic core scales, multidimensional fatigue scale, and cancer module . Cancer . 2002 ; 94 7 : 2090 – 2106 . Google Scholar Crossref Search ADS PubMed WorldCat 70 Varni JW , Seid M , Kurtin PS. PedsQL 4.0: Reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations . Med Care . 2001 ; 39 8 : 800 – 812 . Google Scholar Crossref Search ADS PubMed WorldCat 71 Diorio C , Schechter T , Lee M , et al. . A pilot study to evaluate the feasibility of individualized yoga for inpatient children receiving intensive chemotherapy . BMC Complement Altern Med . 2015 ; 15 1 : 2. Google Scholar Crossref Search ADS PubMed WorldCat 72 Fiuza-Luces C , Padilla JR , Valentin J , et al. . Effects of exercise on the immune function of pediatric patients with solid tumors: insights from the PAPEC randomized trial . Am J Phys Med Rehabil . 2017 ; 96 11 : 831 – 837 . Google Scholar Crossref Search ADS PubMed WorldCat 73 Ladha AB , Courneya KS , Bell GJ , et al. . Effects of acute exercise on neutrophils in pediatric acute lymphoblastic leukemia survivors: a pilot study . J Pediatr Hematol Oncol . 2006 ; 28 10 : 671 – 677 . Google Scholar Crossref Search ADS PubMed WorldCat 74 Shore S , Shepard RJ. Immune responses to exercise in children treated for cancer . J Sports Med Phys Fitness . 1999 ; 39 3 : 240 – 243 . Google Scholar PubMed WorldCat 75 Chamorro-Vina C , Ruiz JR , Santana-Sosa E , et al. . Exercise during hematopoietic stem cell transplant hospitalization in children . Med Sci Sports Exerc . 2010 ; 42 6 : 1045 – 1053 . Google Scholar PubMed WorldCat 76 Chamorro-Vina C , Valentin J , Fernandez L , et al. . Influence of a moderate-intensity exercise program on early NK cell immune recovery in pediatric patients after reduced-intensity hematopoietic stem cell transplantation . Integr Cancer Ther . 2017 ; 16 4 : 464 – 472 . Google Scholar Crossref Search ADS PubMed WorldCat 77 Smith WA , Ness KK , Joshi V , et al. . Exercise training in childhood cancer survivors with subclinical cardiomyopathy who were treated with anthracyclines . Pediatr Blood Cancer . 2013 ;61(5):10.1002/pbc.24850. WorldCat 78 Jarvela LS , Niinikoski H , Heinonen OJ , et al. . Endothelial function in long-term survivors of childhood acute lymphoblastic leukemia: effects of a home-based exercise program . Pediatr Blood Cancer . 2013 ; 60 9 : 1546 – 1551 . Google Scholar Crossref Search ADS PubMed WorldCat 79 Long TM , Rath SR , Wallman KE , et al. . Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult . PLoS One . 2018 ; 13 8 : e0201449. Google Scholar Crossref Search ADS PubMed WorldCat 80 Riggs L , Piscione J , Laughlin S , et al. . Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training . Neuro Oncol . 2017 ; 19 3 : 440 – 450 . Google Scholar PubMed WorldCat 81 Szulc-Lerch KU , Timmons BW , Bouffet E , et al. . Repairing the brain with physical exercise: cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention . Neuroimage Clin . 2018 ; 18 : 972 – 985 . Google Scholar Crossref Search ADS PubMed WorldCat 82 Muller C , Winter C , Boos J , et al. . Effects of an exercise intervention on bone mass in pediatric bone tumor patients . Int J Sports Med . 2014 ; 35 8 : 696 – 703 . Google Scholar Crossref Search ADS PubMed WorldCat 83 Ruiz JR , Fleck SJ , Vingren JL , et al. . Preliminary findings of a 4-month intrahospital exercise training intervention on IGFs and IGFBPs in children with leukemia . J Strength Cond Res . 2010 ; 24 5 : 1292 – 1297 . Google Scholar Crossref Search ADS PubMed WorldCat 84 Cox CL , Zhu L , Kaste SC , et al. . Modifying bone mineral density, physical function, and quality of life in children with acute lymphoblastic leukemia . Pediatr Blood Cancer . 2018 ; 65 4 : e26929 . Google Scholar Crossref Search ADS WorldCat 85 Mogil RJ , Kaste SC , Ferry RJ Jr , et al. . Effect of low-magnitude, high-frequency mechanical stimulation on BMD among young childhood cancer survivors . JAMA Oncol . 2016 ; 2 7 : 908 – 914 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JNCI Monographs Oxford University Press

Dietary and Exercise Interventions for Pediatric Oncology Patients: The Way Forward

JNCI Monographs , Volume 2019 (54) – Sep 1, 2019

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Oxford University Press
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© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
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1052-6773
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1745-6614
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10.1093/jncimonographs/lgz021
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Abstract

Abstract This review focuses on diet and exercise interventions that have been conducted in pediatric cancer and pediatric stem cell transplant patients. It examines the different reasons for conducting lifestyle interventions with attention to the different outcome measurements and feasibility of these measures with an argument toward a need for standardization to move the field forward. Pediatric cancer now has a 5-year survival rate of more than 80%. Thus, there is a growing number of long-term survivors at risk for therapy-related complications. These include obesity and predisposition to the metabolic syndrome in those exposed to cranial radiation and steroids (1,2). Many pediatric cancer patients are deconditioned at diagnosis; fitness and loss of lean body mass often worsen on therapy and persist into long-term follow-up (3–5). Additionally, malnutrition and/or obesity from disease, treatment exposure, and illness-related poor eating habits potentially impact chances of oncologic cure (6). Finally, the pediatric cancer experience can cause psychological strain, negatively impacting health-related quality of life (HRQOL) (3). Fortunately, these disease- and therapy-related conditions are potentially responsive to diet and exercise interventions. Attempts to find unifying best practices for lifestyle interventions in childhood cancer patients are hampered by lack of large randomized data, diversity of outcomes, and heterogeneous treatment strategies, making it difficult to draw solid conclusions (7–11). This review describes existing interventions and outcome measures for pediatric oncology patients, with special attention intervention feasibility as it relates to setting and timing, and provides suggestions for future trials. Dietary Interventions in Pediatric Cancer Modifying nutritional intake has benefits for everyone including maximizing chances of disease cure, preventing infection, and managing body composition before it perpetuates as obesity during survivorship. Unfortunately, surveys indicate that nutritional services are inconsistent across pediatric oncology centers; not all patients get assistance in maintaining a healthy diet (12,13) Recent evidence suggests that being overweight during treatment for acute lymphoblastic leukemia increases risk of persistent disease and relapse (6,14), which really requires a paradigm shift for nutrition management during therapy. Because children typically lose weight during initial intense phases of treatment, the focus has traditionally been on optimizing calories. However, 36% of children are overweight when diagnosed with acute lymphoblastic leukemia, and 79% consume more than recommended total calories (1,15). Maintenance of normal body mass index (BMI) and weight gain are accompanied by gains in body fat percentage, often with corresponding loss in lean mass (sarcopenic obesity) (16) due to the toxicity of specific treatment modalities and compounded by inactivity. In fact, emerging evidence indicates that caloric intake actually decreases in the most common pediatric cancer populations (acute lymphoblastic leukemia [ALL] and central nervous system tumors) during therapy but fat intake increases, thus a focus on the quality of nutritional intake should be prioritized over total calories (1,17,18). Nutritional interventions during therapy have yielded only modest results, most have been limited to children with ALL, and none have evaluated the impact of the intervention on survival. One study implemented a nutritional counseling program in 22 pediatric ALL patients during maintenance chemotherapy (12 in intervention group) over a year, with a resultant decrease in caloric intake but no changes in body weight or waist circumference (19). Another trial used a phone counseling intervention promoting healthy eating and physical activity, targeting caregivers of pediatric cancer patients (n = 53; 27 in intervention group) (20). Modest reductions in caloric intake among caregivers and in sugary beverage consumption among children were reported. Both caregivers and children had modest reductions in BMI. Two other randomized studies that added nutritional education to physical activity interventions, one during maintenance chemotherapy for ALL (21) and one after completion of ALL therapy (22), had no impact on weight, even in the presence of increased physical activity. Patients with obesity caused by tumors involving the hypothalamus often struggle to lose weight despite dietary interventions. One comprehensive clinic demonstrates that weight gain can be mitigated by a multidisciplinary approach focused on social skills classes, cognitive behavior therapy, and motivational interviewing (23). Barriers to Successful Nutrition Interventions There are several barriers that prevent successful implementation of nutritional interventions. First, although there are many national recommendations for healthy eating, there are no standard programs for recommended nutritional intake during cancer therapy. As a result, it is challenging to set benchmarks for ideal intake and to know which components of dietary intake should be targeted during treatment (12). Secondly, most dietary intake interventions to date have focused on the patient only (10). Because a patient’s dietary intake is often dependent on what their family is eating, patients might not have the opportunity to make healthy choices if they are not available in the family’s meal and/or snack repertoire. Thus, family-based approaches are the most likely to result in successful change and/or choice. Finally, dietary intake varies greatly between individuals, with reasons for suboptimal (too little, too much, the wrong foods) dietary intake dependent on age, preference, religion, altered taste related to chemotherapy administration, nausea, and parent’s desire to provide something for their sick child. Interventions will have to incorporate individualized nutrition plans in the context of reproduceable and evaluable nutritional guidelines. Specific Nutritional Modifications Prescribing a neutropenic diet (avoiding raw vegetables and fresh deli meats), conceived to prevent infections in pediatric oncology patients by limiting introduction of bacteria into the gastrointestinal tract (24), is not uncommon in practice (25), even though data from a randomized study (n = 150) indicate that there is no difference in infection rates in patients using a neutropenic diet compared to those who followed Food and Drug Administration food safety guidelines (24). Furthermore, emerging evidence indicates that bacteria in the microbiome may actually help prevent infections. There is little data to support other diet modifications during therapy other than a case series indicating feasibility of a high-fat, low-carbohydrate diet, often used to treat refractory seizures, in pediatric brain tumor patients (26). A summary of key nutritional recommendations for the way forward is given in Table 1. Table 1. Key recommendations for dietary intake studies Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Open in new tab Table 1. Key recommendations for dietary intake studies Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Maintaining a healthy weight is important for both general heath but also can impact the chance of cancer cure. Body mass index should not be the only assessment of healthy weight because cancer patients often have sarcopenic obesity (increased fat mass percentage with decrease in lean muscle mass). Current published dietary interventions studies have only shown a minor impact in weight changes. Ideal nutrition goals for pediatric cancer patients need to be defined. Nutritional interventions that target the whole family may increase the chances of success. When designing an intervention, balancing the individual needs of a given patient with creating a reproducible and evaluable intervention is needed. Open in new tab Barriers to Successful Exercise Interventions Exercise is good for everyone including children with cancer, given their increased risk of premature cardiovascular disease and mortality (27). However, there are some barriers that make exercise difficult. A pediatric cancer diagnosis is a major life event. Appropriate focus on cure stresses families and leads to complications such as unemployment, divorce, and home relocation, all which make it difficult to incorporate exercise into a daily routine (28). Although parents often recognize that their children are overweight, most do not remember that their oncologist discussed potential complications of being overweight (29). Other barriers reported by patients and families include being too tired, too busy, afraid of injury, and lack of access to exercise resources and having negative thoughts and feelings about themselves (30). Exercise trials remove some of these barriers (access, fear of injury) but are difficult to conduct in families disrupted and consumed by the intensity of cancer therapy (30,31). Another potential barrier to exercise is asking the patient to be active when their family is not. As with nutritional interventions, physical activity interventions are most likely to be successful when the entire family is included. Designing a feasible and successful intervention is challenging and requires input from family stakeholders in terms of when to intervene, where to intervene (venue), and what an acceptable time commitment would be. Exercise Interventions Targeting Body Composition Weight loss is a common aim in exercise interventions. However, in 12 studies, no statistically significant weight loss occurred in the intervention group, and in 6 randomized trials delivered during active ALL therapy, weight gain occurred regardless of group assignment (21,22,32–41), In addition, inclusion criteria, intervention timing, and measurement techniques are not uniform. Positive findings include one study among patients whose BMI was above the 85th percentile, where rate of BMI gain (height and weight measurements) during therapy was less in those in the exercise group than in the control group (22), another that demonstrated loss of fat mass (dual x-ray absorptiometry measurement) during the first 2 years after therapy among children with ALL who were randomly assigned to exercise during therapy when compared to control subjects (35), and one that showed statistically significant decreases in overall and abdominal body fat (skinfold and waist circumference measurements) in 17 ALL survivors after a 16-week exercise intervention (36). Further study is needed to establish inclusion criteria (targeting those at greatest risk), to identify the most appropriate timing for intervention, and to determine the best body mass assessment tool. Exercise Interventions Targeting Physical Deconditioning Physical deconditioning in children with cancer includes loss of strength, flexibility, fitness, and mobility, all which result from or contribute to inactivity. Evaluating the effects of interventions on these outcomes is challenging, because studies (n = 36; 30 in cancer, 6 in stem cell transplant [SCT]) are small (mean = 28, subjects range = 6–97) and use heterogeneous measurement tools and outcome assessment timing (21,22,32–65). In addition, adherence to different exercise interventions varies from 25% to 100%, making it difficult to determine if null results are associated with poor adherence or the result of inadequate exercise dose. Adherence was highest in studies where the exercise was directly observed by study personnel, or when conducted in an inpatient setting as opposed to in-home settings. Nevertheless, home or community-based interventions are necessary, because it is difficult to translate labor-intensive and costly supervised or hospital-based programs into most clinical settings. Increasing physical activity is a focus for many exercise interventions. Sedentary and active behavior can be measured objectively using accelerometers, now incorporated into most smart phones. Accelerometer data are hard to evaluate. Complete data require full time wear, and children frequently forget to wear them, or lose them. Nevertheless, they do provide objective data. Self-report or exercise logs are also used to evaluate activity but provide less reliable estimates (37,53,65) or have low adherence (46,65), respectively. Of 11 studies that used accelerometers, 10 showed no statistically significant change in moderate-to-vigorous activity for the intervention group when compared to control subjects (21,22,32,34,48–50,52,53,57,63). Although these data are discouraging, sensor technology is improving. Newer devices (66) that stick to the body and have prolonged durability, or data captured on smart phones typically carried everywhere, may be a better way to capture movement-derived data. Other goals of exercise interventions are to improve flexibility, strength, and motor function. Ankle range of motion, a common problem for children with ALL, has been evaluated with goniometry in 10 studies, with 3 showing some improvement in the intervention group (32,51,61), 1 showing worsening (35), and the rest showing no significant change (32,33,35,38–40,46,51,61,64). General flexibility was assessed in three studies (one improvement) using the sit-and-reach test (21,33,64,67). Handheld dynamometers or ability to lift increasing weight loads are used to measure strength. Knee extension (six studies used, three showing improvement); hip abduction (three studies, one improvement); handgrip (six studies, three improvement); shoulder flexion (two studies, no change) (32,33,40–42,46,50,51,56); and increases in weight load (four studies, three improvement) (34,38,39,54) have been measured. The Bruininks-Oseretsky Test of Motor Proficiency was used to test motor function in three studies. Statistically Significant improvement in response to exercise was reported in two (33,55,57). Psychometric assessment to determine an optimal set of tests to evaluate flexibility, strength, and motor function in children with cancer would improve interpretability of studies. Fitness and functional mobility are also exercise intervention targets. Fitness assessment by evaluating peak oxygen uptake on cycle ergometers (four studies, one showing improvement) or treadmills (two studies, both showing improvement) is the gold standard but is time intensive and may be difficult for children who are deconditioned (32,38–40,55,68). Walk tests—distance walked in a predetermined number of minutes—are also used to assess fitness (eight studies, six improvement) (33,41,42,51,53,59,60,62). Walk tests require an open hallway clear of obstacles, are effort dependent, and again may be difficult for deconditioned children. Functional mobility is evaluated with the Timed Up and Go Test—the time to stand from a chair, walk 10 feet and return to sitting (seven studies, three improvement) (34,38–41,60,64), or the Timed Up and Down Stairs—the time required to ascend and descend one flight of a standard staircase (seven studies, two improvement) (34,38–41,51,60). Like the walk tests, these measures of functional mobility are easy to perform but are effort dependent and require a motivated child. Exercise Interventions Targeting HRQOL HRQOL is also a target of pediatric oncology exercise interventions (69,70). The most commonly used measure to date is the 23-item Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale (69). It was designed for ages 2–18 years and uses both child reporting and parent proxy to assess physical, emotional, social, and school functioning. Fourteen exercise intervention (five randomized) studies in children with cancer have used this measure. These vary by sample size (6–69 participants), type of exercise (11 traditional, 3 yoga), encompass all phases of treatment (newly diagnosed, long-term survivorship), use of proxies, and frequency of reporting (time between assessments 3 weeks–18 months) (32,37,43,45–47,50,51,54,59,60,64,71). Seven studies showed improvement in at least 1 domain. In one study, the exercise intervention was delivered early in leukemia therapy. HRQOL decreased as therapy became more intense (47). In another study, authors found no difference in HRQOL between exercise and control groups as they progressed further out from end of therapy (32), illustrating the difficulty of evaluating effects of exercise interventions on HRQOL, an outcome largely influenced by cancer treatment intensity. Two other common patient and/or proxy reported outcome measures are the 27-item PedsQL 3.0 Cancer Module (69), which assesses pain and/or injury, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication, and the 18-item Multidimensional Fatigue Inventory, which assesses general, sleep and/or rest, and cognitive fatigue. Just one of four exercise intervention studies in children with cancer demonstrated improvement on the PedsQL 3.0 Cancer Module or the Multidimensional Fatigue Inventory as a result of the intervention, and gains were likely not clinically signficant (32,34,37,54,56,59,60,65,71). Many other measures have been employed. In all cases, these measurements have been evaluated to be feasible, but standardization is needed across trials for these measurements to be comparable. Exercise Interventions Targeting Other Cancer Comorbidities Exercise has other potential benefits that could prevent or mitigate complications of pediatric cancer therapy, including immune system dysfunction, cardiac toxicity, and neural recovery, and bone mineral density. Data are preliminary, but somewhat positive. Five studies with 6–10 patients in the exercise group resulted in an association between exercise and a boost in neutrophil count among children with cancer (72–74), a small increase in natural killer cell cytotoxicity by boosting CD56dim cells, and mitigation of fall in dendritic cell counts among children after stem cell transplantation (75,76). Among survivors exposed to anthracyclines, Smith et al. (77) demonstrated that exercise is safe among those with reduced ejection fraction. Studies also indicate that that exercise can improve endothelial structures and function and peak circumferential systolic and diastolic strain (68,78,79). Among pediatric brain tumor survivors, exercise is associated with increasing brain white matter, hippocampal volume, and cortical thickness (80,81). Studies evaluating the effects of exercise on bone mineral density and metabolic function in children with cancer and among survivors are largely null with small sample sizes and poor intervention adherence (82–84). One randomized study, using low-magnitude mechanical stimulation as an exercise mimetic, did have a statistically and clinically meaningful (0.5 standard deviations) effect on bone mineral density in children and adolescents with low bone mineral density after completion of cancer therapy (85). There is a need for more studies with larger sample sizes of the effects of exercise on immune function, cardiovascular health, neural recovery, bone density, and metabolic health in pediatric oncology patients. A summary of key exercise recommendations for the way forward is given in Table 2. Table 2. Key recommendations for exercise intervention studies Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Open in new tab Table 2. Key recommendations for exercise intervention studies Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Exercise is good for all and can help prevent premature cardiovascular disease and mortality. During cancer, patients often feel sick and are deconditioned, therefore, it is challenging to design interventions that are feasible. Targeting exercise intervention to the whole family unit could increase success. Weight loss is difficult to achieve with exercise interventions alone. Evaluating changes in physical activity, functional mobility, and fitness as endpoints for an exercise intervention are effective outcomes to demonstrate improvement; however, both standardization and better definitions of clinically significant outcomes are needed. Measuring changes in health-related quality of life and fatigue can also give objective evidence of impact for an exercise intervention; however, standardization and establishing a metric for clinically significant outcomes is needed. Exercise has additional health benefits and further study into how it impacts the immune system, heart, brain, and bones is needed. Open in new tab Diet and exercise interventions are feasible in the pediatric oncology and SCT populations, however, there are many study design issues and barriers to participation that need to be overcome. There are many compelling reasons for conducting these interventions, and when designing new interventions, consideration should be made to pick outcomes that are reliable and reproducible. Standardization of outcome measures is needed so that studies can be compared and combined. Notes Affiliations of authors: Vanderbilt-Ingram Cancer Center, Nashville, TN (AJE); Monroe Carell Jr. Children’s Hospital at Vanderbilt Division of Pediatric Hematology-Oncology, Nashville, TN (AJE); Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN (KKN). The authors have no conflicts of interest to report. References 1 Esbenshade AJ , Simmons JH , Koyama T , et al. . Body mass index and blood pressure changes over the course of treatment of pediatric acute lymphoblastic leukemia . Pediatr Blood Cancer . 2011 ; 56 3 : 372 – 378 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Esbenshade AJ , Simmons JH , Koyama T , et al. . Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy . Pediatr Blood Cancer . 2013 ; 60 8 : 1287 – 1291 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Deisenroth A , Sontgerath R , Schuster AJ , et al. . Muscle strength and quality of life in patients with childhood cancer at early phase of primary treatment . Pediatr Hematol Oncol . 2016 ; 33 6 : 393 – 407 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Ness KK , DeLany JP , Kaste SC , et al. . Energy balance and fitness in adult survivors of childhood acute lymphoblastic leukemia . Blood . 2015 ; 125 22 : 3411 – 3419 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Ness KK , Kaste SC , Zhu L , et al. . Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia . Leuk Lymphoma . 2015 ; 56 4 : 1004 – 1011 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Orgel E , Tucci J , Alhushki W , et al. . Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia . Blood . 2014 ; 124 26 : 3932 – 3938 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Braam KI , van der Torre P , Takken T , et al. . Physical exercise training interventions for children and young adults during and after treatment for childhood cancer . Cochrane Database Syst Rev . 2016 ; 3 : CD008796. Google Scholar PubMed WorldCat 8 Morales JS , Valenzuela PL , Rincon-Castanedo C , et al. . Exercise training in childhood cancer: a systematic review and meta-analysis of randomized controlled trials . Cancer Treat Rev . 2018 ; 70 : 154 – 167 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Oberoi S , Robinson PD , Cataudella D , et al. . Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: a systematic review and meta-analysis of randomized trials . Crit Rev Oncol Hematol . 2018 ; 122 : 52 – 59 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Raber M , Swartz MC , Santa Maria D , et al. . Parental involvement in exercise and diet interventions for childhood cancer survivors: a systematic review . Pediatr Res . 2016 ; 80 3 : 338 – 346 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Wang KW , Chau R , Fleming A , et al. . The effectiveness of interventions to treat hypothalamic obesity in survivors of childhood brain tumours: a systematic review . Obes Rev . 2017 ; 18 8 : 899 – 914 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Ladas EJ , Sacks N , Brophy P , et al. . Standards of nutritional care in pediatric oncology: results from a nationwide survey on the standards of practice in pediatric oncology. A Children’s Oncology Group study . Pediatr Blood Cancer . 2006 ; 46 3 : 339 – 344 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Selwood K , Ward E , Gibson F. Assessment and management of nutritional challenges in children’s cancer care: a survey of current practice in the United Kingdom . Eur J Oncol Nurs . 2010 ; 14 5 : 439 – 446 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Orgel E , Genkinger JM , Aggarwal D , et al. . Association of body mass index and survival in pediatric leukemia: a meta-analysis . Am J Clin Nutr . 2016 ; 103 3 : 808 – 817 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Ladas EJ , Orjuela M , Stevenson K , et al. . Dietary intake and childhood leukemia: the Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) cohort study . Nutrition . 2016 ; 32 10 : 1103 – 1109 e1 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Orgel E , Mueske NM , Sposto R , et al. . Limitations of body mass index to assess body composition due to sarcopenic obesity during leukemia therapy . Leuk Lymphoma . 2018 ; 59 1 : 138 – 145 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Ladas EJ , Orjuela M , Stevenson K , et al. . Fluctuations in dietary intake during treatment for childhood leukemia: a report from the DALLT cohort . [published online ahead of print March 1, 2019]. Clin Nutr . 2019 . doi:10.1016/j.clnu.2018.12.021. WorldCat 18 Bakish J , Hargrave D , Tariq N , et al. . Evaluation of dietetic intervention in children with medulloblastoma or supratentorial primitive neuroectodermal tumors . Cancer . 2003 ; 98 5 : 1014 – 1020 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Li R , Donnella H , Knouse P , et al. . A randomized nutrition counseling intervention in pediatric leukemia patients receiving steroids results in reduced caloric intake . Pediatr Blood Cancer . 2017 ; 64 2 : 374 – 380 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Stern M , Bleck J , Ewing LJ , et al. . NOURISH-T: targeting caregivers to improve health behaviors in pediatric cancer survivors with obesity . Pediatr Blood Cancer . 2018 ; 65 5 : e26941. Google Scholar Crossref Search ADS PubMed WorldCat 21 Moyer-Mileur LJ , Ransdell L , Bruggers CS. Fitness of children with standard-risk acute lymphoblastic leukemia during maintenance therapy: response to a home-based exercise and nutrition program . J Pediatr Hematol Oncol . 2009 ; 31 4 : 259 – 266 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Huang JS , Dillon L , Terrones L , et al. . Fit4Life: a weight loss intervention for children who have survived childhood leukemia . Pediatr Blood Cancer . 2014 ; 61 5 : 894 – 900 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Rakhshani N , Jeffery AS , Schulte F , et al. . Evaluation of a comprehensive care clinic model for children with brain tumor and risk for hypothalamic obesity . Obesity (Silver Spring) . 2010 ; 18 9 : 1768 – 74 . Google Scholar Crossref Search ADS PubMed WorldCat 24 Moody KM , Baker RA , Santizo RO , et al. . A randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patients . Pediatr Blood Cancer . 2018 ; 65 1 : e26711. Google Scholar Crossref Search ADS WorldCat 25 Braun LE , Chen H , Frangoul H. Significant inconsistency among pediatric oncologists in the use of the neutropenic diet . Pediatr Blood Cancer . 2014 ; 61 10 : 1806 – 1810 . Google Scholar Crossref Search ADS PubMed WorldCat 26 Nebeling LC , Miraldi F , Shurin SB , et al. . Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports . J Am Coll Nutr . 1995 ; 14 2 : 202 – 208 . Google Scholar Crossref Search ADS PubMed WorldCat 27 Scott JM , Li N , Liu Q , et al. . Association of exercise with mortality in adult survivors of childhood cancer . JAMA Oncol . 2018 ; 4 10 : 1352 – 1358 . Google Scholar Crossref Search ADS PubMed WorldCat 28 Lau S , Lu X , Balsamo L , et al. . Family life events in the first year of acute lymphoblastic leukemia therapy: a children’s oncology group report . Pediatr Blood Cancer . 2014 ; 61 12 : 2277 – 2284 . Google Scholar Crossref Search ADS PubMed WorldCat 29 Jones GL , McClellan W , Raman S , et al. . Parental perceptions of obesity and obesity risk associated with childhood acute lymphoblastic leukemia . J Pediatr Hematol Oncol . 2017 ; 39 5 : 370 – 375 . Google Scholar Crossref Search ADS PubMed WorldCat 30 Ross WL , Le A , Zheng DJ , et al. . Physical activity barriers, preferences, and beliefs in childhood cancer patients . Support Care Cancer . 2018 ; 26 7 : 2177 – 2184 . Google Scholar Crossref Search ADS PubMed WorldCat 31 van Dijk-Lokkart EM , Braam KI , Huisman J , et al. . Factors influencing childhood cancer patients to participate in a combined physical and psychosocial intervention program: quality of life in motion . Psychooncology . 2015 ; 24 4 : 465 – 471 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Braam KI , van Dijk-Lokkart EM , Kaspers GJL , et al. . Effects of a combined physical and psychosocial training for children with cancer: a randomized controlled trial . BMC Cancer . 2018 ; 18 1 : 1289. Google Scholar Crossref Search ADS PubMed WorldCat 33 Esbenshade AJ , Friedman DL , Smith WA , et al. . Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia . Pediatr Phys Ther . 2014 ; 26 3 : 301 – 307 . Google Scholar Crossref Search ADS PubMed WorldCat 34 Fiuza-Luces C , Padilla JR , Soares-Miranda L , et al. . Exercise intervention in pediatric patients with solid tumors: the physical activity in pediatric cancer trial . Med Sci Sports Exerc . 2017 ; 49 2 : 223 – 230 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Hartman A , Te Winkel ML , van Beek RD , et al. . A randomized trial investigating an exercise program to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukemia . Pediatr Blood Cancer . 2009 ; 53 1 : 64 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Jarvela LS , Kemppainen J , Niinikoski H , et al. . Effects of a home-based exercise program on metabolic risk factors and fitness in long-term survivors of childhood acute lymphoblastic leukemia . Pediatr Blood Cancer . 2012 ; 59 1 : 155 – 160 . Google Scholar Crossref Search ADS PubMed WorldCat 37 Keats MR , Culos-Reed SN. A community-based physical activity program for adolescents with cancer (project TREK): program feasibility and preliminary findings . J Pediatr Hematol Oncol . 2008 ; 30 4 : 272 – 280 . Google Scholar Crossref Search ADS PubMed WorldCat 38 San Juan AF , Chamorro-Vina C , Moral S , et al. . Benefits of intrahospital exercise training after pediatric bone marrow transplantation . Int J Sports Med . 2008 ; 29 5 : 439 – 446 . Google Scholar Crossref Search ADS PubMed WorldCat 39 San Juan AF , Fleck SJ , Chamorro VC , et al. . Effects of an intrahospital exercise program intervention for children with leukemia . Med Sci Sports Exerc . 2007 ; 39 1 : 13 – 21 . Google Scholar Crossref Search ADS PubMed WorldCat 40 Takken T , van der Torre P , Zwerink M , et al. . Development, feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors . Psychooncology . 2009 ; 18 4 : 440 – 448 . Google Scholar Crossref Search ADS PubMed WorldCat 41 Yildiz Kabak V , Duger T , Uckan Cetinkaya D. Investigation of the effects of an exercise program on physical functions and activities of daily life in pediatric hematopoietic stem cell transplantation . Pediatr Blood Cancer . 2016 ; 63 9 : 1643 – 1648 . Google Scholar Crossref Search ADS PubMed WorldCat 42 Bogg TF , Broderick C , Shaw P , et al. . Feasibility of an inpatient exercise intervention for children undergoing hematopoietic stem cell transplant . Pediatr Transplantation . 2015 ; 19 8 : 925 – 931 . Google Scholar Crossref Search ADS WorldCat 43 Chung OK , Li HC , Chiu SY , et al. . Sustainability of an integrated adventure-based training and health education program to enhance quality of life among Chinese childhood cancer survivors: a randomized controlled trial . Cancer Nurs . 2015 ; 38 5 : 366 – 374 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Diorio C , Celis Ekstrand A , Hesser T , et al. . Development of an individualized yoga intervention to address fatigue in hospitalized children undergoing intensive chemotherapy . Integr Cancer Ther . 2016 ; 15 3 : 279 – 284 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Geyer R , Lyons A , Amazeen L , et al. . Feasibility study: the effect of therapeutic yoga on quality of life in children hospitalized with cancer . Pediatr Phys Ther . 2011 ; 23 4 : 375 – 379 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Gilliam MB , Ross K , Futch L , et al. . A pilot study evaluation of a web-based token economy to increase adherence with a community-based exercise intervention in child and adolescent cancer survivors . Rehabil Oncol . 2011 ; 29 2 : 16 – 22 . Google Scholar Crossref Search ADS WorldCat 47 Gohar SF , Comito M , Price J , et al. . Feasibility and parent satisfaction of a physical therapy intervention program for children with acute lymphoblastic leukemia in the first 6 months of medical treatment . Pediatr Blood Cancer . 2011 ; 56 5 : 799 – 804 . Google Scholar Crossref Search ADS PubMed WorldCat 48 Hinds PS , Hockenberry M , Rai SN , et al. . Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer . J Pain Symptom Manage . 2007 ; 33 6 : 686 – 697 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Hooke MC , Gilchrist L , Tanner L , et al. . Use of a fitness tracker to promote physical activity in children with acute lymphoblastic leukemia . Pediatr Blood Cancer . 2016 ; 63 4 : 684 – 689 . Google Scholar Crossref Search ADS PubMed WorldCat 50 Howell CR , Krull KR , Partin RE , et al. . Randomized web-based physical activity intervention in adolescent survivors of childhood cancer . Pediatr Blood Cancer . 2018 ; 65 8 : e27216. Google Scholar Crossref Search ADS PubMed WorldCat 51 Marchese VG , Chiarello LA , Lange BJ. Effects of physical therapy intervention for children with acute lymphoblastic leukemia . Pediatr Blood Cancer . 2004 ; 42 2 : 127 – 133 . Google Scholar Crossref Search ADS PubMed WorldCat 52 Mendoza JA , Baker KS , Moreno MA , et al. . A Fitbit and Facebook mHealth intervention for promoting physical activity among adolescent and young adult childhood cancer survivors: a pilot study . Pediatr Blood Cancer . 2017 ; 64 12 : e26660 . Google Scholar Crossref Search ADS WorldCat 53 Ovans JA , Hooke MC , Bendel AE , et al. . Physical therapist coaching to improve physical activity in children with brain tumors: a pilot study . Pediatr Phys Ther . 2018 ; 30 4 : 310 – 317 . Google Scholar Crossref Search ADS PubMed WorldCat 54 Perondi MB , Gualano B , Artioli GG , et al. . Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia . J Sports Sci Med . 2012 ; 11 3 : 387 – 392 . Google Scholar PubMed WorldCat 55 Piscione PJ , Bouffet E , Timmons B , et al. . Exercise training improves physical function and fitness in long-term paediatric brain tumour survivors treated with cranial irradiation . Eur J Cancer . 2017 ; 80 : 63 – 72 . Google Scholar Crossref Search ADS PubMed WorldCat 56 Rosenhagen A , Bernhorster M , Vogt L , et al. . Implementation of structured physical activity in the pediatric stem cell transplantation . Klin Padiatr . 2011 ; 223 3 : 147 – 151 . Google Scholar Crossref Search ADS PubMed WorldCat 57 Sabel M , Sjolund A , Broeren J , et al. . Active video gaming improves body coordination in survivors of childhood brain tumours . Disabil Rehabil . 2016 ; 38 21 : 2073 – 2084 . Google Scholar Crossref Search ADS PubMed WorldCat 58 Speyer E , Herbinet A , Vuillemin A , et al. . Effect of adapted physical activity sessions in the hospital on health-related quality of life for children with cancer: a cross-over randomized trial . Pediatr Blood Cancer . 2010 ; 55 6 : 1160 – 1166 . Google Scholar Crossref Search ADS PubMed WorldCat 59 Su HL , Wu LM , Chiou SS , et al. . Assessment of the effects of walking as an exercise intervention for children and adolescents with cancer: a feasibility study . Eur J Oncol Nurs . 2018 ; 37 : 29 – 34 . Google Scholar Crossref Search ADS PubMed WorldCat 60 Tanir MK , Kuguoglu S. Impact of exercise on lower activity levels in children with acute lymphoblastic leukemia: a randomized controlled trial from Turkey . Rehabil Nurs . 2013 ; 38 1 : 48 – 59 . Google Scholar Crossref Search ADS PubMed WorldCat 61 Tanner L , Sencer S , Hooke MC. The stoplight program: a proactive physical therapy intervention for children with acute lymphoblastic leukemia . J Pediatr Oncol Nurs . 2017 ; 34 5 : 347 – 357 . Google Scholar Crossref Search ADS PubMed WorldCat 62 Wallek S , Senn-Malashonak A , Vogt L , et al. . Impact of the initial fitness level on the effects of a structured exercise therapy during pediatric stem cell transplantation . Pediatr Blood Cancer . 2018 ; 65 2 : e26851 . Google Scholar Crossref Search ADS WorldCat 63 Winter CC , Muller C , Hardes J , et al. . The effect of individualized exercise interventions during treatment in pediatric patients with a malignant bone tumor . Support Care Cancer . 2013 ; 21 6 : 1629 – 1636 . Google Scholar Crossref Search ADS PubMed WorldCat 64 Wurz A , Chamorro-Vina C , Guilcher GM , et al. . The feasibility and benefits of a 12-week yoga intervention for pediatric cancer out-patients . Pediatr Blood Cancer . 2014 ; 61 10 : 1828 – 1834 . Google Scholar Crossref Search ADS PubMed WorldCat 65 Yeh CH , Man Wai JP , Lin US , et al. . A pilot study to examine the feasibility and effects of a home-based aerobic program on reducing fatigue in children with acute lymphoblastic leukemia . Cancer Nurs . 2011 ; 34 1 : 3 – 12 . Google Scholar Crossref Search ADS PubMed WorldCat 66 Levine DM , Ouchi K , Blanchfield B , et al. . Hospital-level care at home for acutely Ill adults: a pilot randomized controlled trial . J Gen Intern Med . 2018 ; 33 5 : 729 – 736 . Google Scholar Crossref Search ADS PubMed WorldCat 67 Huang TT , Ness KK. Exercise interventions in children with cancer: a review . Int J Pediatr . 2011 ; 2011 : 461512. Google Scholar Crossref Search ADS PubMed WorldCat 68 Jarvela LS , Saraste M , Niinikoski H , et al. . Home-based exercise training improves left ventricle diastolic function in survivors of childhood ALL: a tissue doppler and velocity vector imaging study . Pediatr Blood Cancer . 2016 ; 63 9 : 1629 – 1635 . Google Scholar Crossref Search ADS PubMed WorldCat 69 Varni JW , Burwinkle TM , Katz ER , et al. . The PedsQL in pediatric cancer: reliability and validity of the pediatric quality of life inventory generic core scales, multidimensional fatigue scale, and cancer module . Cancer . 2002 ; 94 7 : 2090 – 2106 . Google Scholar Crossref Search ADS PubMed WorldCat 70 Varni JW , Seid M , Kurtin PS. PedsQL 4.0: Reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations . Med Care . 2001 ; 39 8 : 800 – 812 . Google Scholar Crossref Search ADS PubMed WorldCat 71 Diorio C , Schechter T , Lee M , et al. . A pilot study to evaluate the feasibility of individualized yoga for inpatient children receiving intensive chemotherapy . BMC Complement Altern Med . 2015 ; 15 1 : 2. Google Scholar Crossref Search ADS PubMed WorldCat 72 Fiuza-Luces C , Padilla JR , Valentin J , et al. . Effects of exercise on the immune function of pediatric patients with solid tumors: insights from the PAPEC randomized trial . Am J Phys Med Rehabil . 2017 ; 96 11 : 831 – 837 . Google Scholar Crossref Search ADS PubMed WorldCat 73 Ladha AB , Courneya KS , Bell GJ , et al. . Effects of acute exercise on neutrophils in pediatric acute lymphoblastic leukemia survivors: a pilot study . J Pediatr Hematol Oncol . 2006 ; 28 10 : 671 – 677 . Google Scholar Crossref Search ADS PubMed WorldCat 74 Shore S , Shepard RJ. Immune responses to exercise in children treated for cancer . J Sports Med Phys Fitness . 1999 ; 39 3 : 240 – 243 . Google Scholar PubMed WorldCat 75 Chamorro-Vina C , Ruiz JR , Santana-Sosa E , et al. . Exercise during hematopoietic stem cell transplant hospitalization in children . Med Sci Sports Exerc . 2010 ; 42 6 : 1045 – 1053 . Google Scholar PubMed WorldCat 76 Chamorro-Vina C , Valentin J , Fernandez L , et al. . Influence of a moderate-intensity exercise program on early NK cell immune recovery in pediatric patients after reduced-intensity hematopoietic stem cell transplantation . Integr Cancer Ther . 2017 ; 16 4 : 464 – 472 . Google Scholar Crossref Search ADS PubMed WorldCat 77 Smith WA , Ness KK , Joshi V , et al. . Exercise training in childhood cancer survivors with subclinical cardiomyopathy who were treated with anthracyclines . Pediatr Blood Cancer . 2013 ;61(5):10.1002/pbc.24850. WorldCat 78 Jarvela LS , Niinikoski H , Heinonen OJ , et al. . Endothelial function in long-term survivors of childhood acute lymphoblastic leukemia: effects of a home-based exercise program . Pediatr Blood Cancer . 2013 ; 60 9 : 1546 – 1551 . Google Scholar Crossref Search ADS PubMed WorldCat 79 Long TM , Rath SR , Wallman KE , et al. . Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult . PLoS One . 2018 ; 13 8 : e0201449. Google Scholar Crossref Search ADS PubMed WorldCat 80 Riggs L , Piscione J , Laughlin S , et al. . Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training . Neuro Oncol . 2017 ; 19 3 : 440 – 450 . Google Scholar PubMed WorldCat 81 Szulc-Lerch KU , Timmons BW , Bouffet E , et al. . Repairing the brain with physical exercise: cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention . Neuroimage Clin . 2018 ; 18 : 972 – 985 . Google Scholar Crossref Search ADS PubMed WorldCat 82 Muller C , Winter C , Boos J , et al. . Effects of an exercise intervention on bone mass in pediatric bone tumor patients . Int J Sports Med . 2014 ; 35 8 : 696 – 703 . Google Scholar Crossref Search ADS PubMed WorldCat 83 Ruiz JR , Fleck SJ , Vingren JL , et al. . Preliminary findings of a 4-month intrahospital exercise training intervention on IGFs and IGFBPs in children with leukemia . J Strength Cond Res . 2010 ; 24 5 : 1292 – 1297 . Google Scholar Crossref Search ADS PubMed WorldCat 84 Cox CL , Zhu L , Kaste SC , et al. . Modifying bone mineral density, physical function, and quality of life in children with acute lymphoblastic leukemia . Pediatr Blood Cancer . 2018 ; 65 4 : e26929 . Google Scholar Crossref Search ADS WorldCat 85 Mogil RJ , Kaste SC , Ferry RJ Jr , et al. . Effect of low-magnitude, high-frequency mechanical stimulation on BMD among young childhood cancer survivors . JAMA Oncol . 2016 ; 2 7 : 908 – 914 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

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JNCI MonographsOxford University Press

Published: Sep 1, 2019

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