DISCUSSION
The importance of physical activity for individuals during and after cancer care has been increasingly recognized. It has favorable effects on various levels of functioning, encompassing aspects of QoL, mood symptoms, fitness level, muscle strength, body composition, and active attainment of social roles.5,7,8,12,24,30,31 A possible relationship between the level of fitness and the risk of both mortality4 and tumor recurrence11,32has also emerged, and is worth exploring.
We know that adolescent and young adults with cancer are less active than their healthy peers (especially when in hospital), and that many of them experience important morbidities while receiving treatment.3,28,29
Fatigue has multiple dimensions that may involve physical, psychological, social and cognitive aspects of the person affected. Consequences of fatigue causes the inability to engage in everyday life activities and social roles (including educational and work opportunities), mood swings, sleep disturbances, impaired relations, lower academic achievement, and impaired QoL.21,22 Among pediatric patients receiving cancer treatments, fatigue is more prevalent in adolescents, and might be particularly important in this age group.20,33
When interviewed at the baseline, 97.5% of our patients who were active before being diagnosed with cancer reported a substantial decline in their exercising and sports activities compared with their previous levels: the main reasons mentioned for abandoning included fatigue, lack of time, and physical disabilities. It is noteworthy that 42% of these patients suspended their physical activities because they had been told, wrongly, that they were contraindicated for cancer patients. This is a common misconception even among general practitioners.
The purpose of our study was to explore the potential effects of an organized exercise program for children and adolescents at a comprehensive cancer center (where a structured exercise program is available28) on patients’ self-reported HRQoL and fatigue.
Our findings indicate that patients who attended the exercise sessions (our GYM group) perceived a better emotional functioning than those who did not, obtaining significantly better scores especially forfear , sadness , sleeping difficulties , anduncertainty about the future . We know that the benefits of exercising and practicing sports go far beyond physical function endpoints alone, but there are still gaps in our understanding of how they benefit the emotional and social spheres, and resilience as well.13,27 A key finding in a study on a large cohort of childhood cancer survivors was that vigorous exercise was associated with a lower risk of depression, somatization, and cognitive impairment.31 Training for a sports competition might symbolize patients’ return to setting themselves healthy and challenging plans for their future. Endorphins, endocannabinoids, monoamines, and neurotrophins have all been implicated in the euphoric response to endurance running,34 and may reinforce the biological rationale behind some of our findings.35 Other investigations have suggested that cardiorespiratory fitness may directly affect brain function, or have attributed the psychological benefits of exercise to improvements in sleep duration or quality.36
Looking at the positive effects of exercising on emotionalhealth, martial arts classes that were recently added to our in-hospital exercise programs13 have proved an interesting way to empower our patients emotionally too, improving their breathing and relaxation skills. During these classes, most of the work aims to help young patients to cope with feelings of pain, anger, anxiety, fear, loss of control, and diminished self-esteem. Interestingly, a panel of experts made a strong recommendation for the use of relaxation techniques or mindfulness, or both, to manage cancer-related fatigue, based on consistent findings concerning the benefits of these practices across different types of adult patients and intervention.23
A better emotional health and self-esteem can also relate to a better social functioning. Patients in our GYM group had better scores for some items referring to social functioning (e.g.getting along with peers , making friends ). For adolescents especially, the benefits of engaging in sports might include regaining a sense of having a lively, properly-functioning body, enhancing relationship with peers and a sense of independence. These findings are in line with research demonstrating positive relationships between physical activity and cognitive outcomes.24–26,37
For the youngest children, integrating physical education in hospital routines may also be important not only to promote physiological motor development,38,39 but also to preserve or restore a normality that cancer patients often lack, such as a chance to play with friends like during gym classes at school. It is important to identify approaches to patients’ safe practice of physical activities, taking into account their age-specific preferences. We know that encouraging physical activity in small children is challenging, but we found that children as young as 5 years old could take an active part in the workout sessions considered in the present study.
On the other hand, our GYM group had worse scores than the No-GYM group for the item that concerned being able to do what peers can do . In principle, everybody can find a suitable form of exercise or sport to practice, though a delicate balance has to be struck between individuals’ wishes and their capabilities (which may have been irreparably affected by their cancer). This may demand adapting certain sports to patients with disabilities, or providing parallel psychological support in some circumstances. Asking patients to exercise may exacerbate their frustrations if the demands placed on them exceed their expected capabilities, especially if prescribed levels of physical fitness are aligned with those enjoyed by a patient before they were diagnosed with cancer.
Our two groups (GYM and No-GYM) differed in terms of cancer types. Indeed patients with brain tumors – who are known to suffer from neuromotor impairments40 - seemed more reluctant to attend the gym (6 out of 8 such patients refused). Professionally-supervised programs need to be developed to accommodate underlying organ system impairments, so that alternative, customized workouts can be used to exercise the less impaired parts of a patient’s body. It is worth noting, for instance, how any lower limb impairment preventing a patient from walking tended to be misconceived as a major reason for not exercising at all because such patients were unable to walk, run, jump, or kick a ball (but they could work out effectively with their upper limbs and trunk).
The strengths of our study include our having examined several dimensions of HRQoL and fatigue, and the correlations between the three dimensions of physical health, psychological functioning and fatigue as a whole. Individuals who have a more positive perception of their neurocognitive functioning may also experience greater self-efficacy, and this would make it easier for them to engage in exercising. The direct correlation identified in our sample between a better perceived physical functioning and a greater perception of fatigue probably stems from the fact that patients motivated to exercise and try to overcome their limits also had a more acute awareness of these limits and their sense of fatigue.
Our findings indicate that children attending the gym scored worse on fatigue, except for general fatigue . Analyzing the single items in the questionnaire showed that the median scores were better in the GYM group for perceived quality of sleep and daily fatigue . The effect of exercise on the severity of fatigue may differ, depending on the type of activity involved (aerobic, neuromotor, or combined exercises might be more effective in containing fatigue than resistance exercises23), and the intensity of the exercise. Given the very heterogeneous nature of cancer populations, recent publications have called for a more precise manipulation of training variables - such as volume, intensity, and frequency - to truly optimize clinically-relevant patient-reported outcomes.10 We did not homogeneously prescribe or record the training parameters adopted in our sample, however, so we are unable to say which type of exercise might be best exercise for the study outcomes, or why scores for fatigue were worse for the GYM group.
There are other limitations in our study to acknowledge. Patients were assigned to one of the two groups being compared not randomly, but based on their volunteering for the exercise program. The patients’ reasons for attending the training sessions may have been positively or negatively influenced by their ability (or fear of inability) to cope with the exercises, or by their attitude to sports before becoming ill (although a similar proportion of patients in the GYM and No-GYM groups had not exercised regularly before being diagnosed with cancer). Our patients also formed a very heterogeneous group, with ages ranging from 5 to 21 years. They had different types of solid tumor, and received different treatments, sometimes involving surgery and radiotherapy as well as chemotherapy (which was administered to all participants in the study). This means that any differences between the GYM and No-GYM groups may not be attributable to our exercise program alone, but also to other factors not assessed (e.g., changes in health status, medication, or other cancer treatments).
A further limitation includes the fact that no longitudinal data were available (to enable any within-subject comparison between before and after the 6-week exercise program in the self-reported QoL outcomes for patients in the GYM group).
We hope our findings will attract attention to the feasibility and possible benefits of promoting more systematic opportunities to move and exercise for young cancer patients, even during their active treatment, to improve their self-reported physical and psychosocial symptoms and HRQoL, and especially their emotional functioning. It is likely that keeping physically active helps. The results of our baseline survey also suggest that many young patients with cancer, their parents, and their doctors feel that a diagnosis of cancer makes it unsafe or unfeasible to exercise and practice sports, but this is a modifiable barrier.
CONFLICTS OF INTEREST STATEMENT: The authors have no conflict of interest to disclose.
AVAILABILITY OF DATA AND MATERIAL  The datasets generated and/or analyzed as part of the present study are available from the corresponding author on reasonable request.
ACKNOWLEDGMENTS: We thank the Associazione Bianca Garavaglia Onlus for their constant financial support. We are also grateful to Gloria and Pasquale, sport professionals, who assist our patients with tailored workouts and constant commitment. The research was partially supported by a private grant from the Associazione Bianca Garavaglia onlus  (salaries for sports professionals).