Predictors of low and very low bone mineral density in long-term childhood acute lymphoblastic leukemia survivors: Toward personalized risk prediction.

BACKGROUND: Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) 10 years after diagnosis. We investigated risk factors for low BMD in long-term cALL survivors. METHODS: We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5 years of event-free survival. Median time since diagnosis was 15.1 years. RESULTS: Prevalence of low DXA-derived BMD (Z-score ≤-1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and between 3.7% and 5.8% for very low BMD (Z-score ≤-2). Males had a higher prevalence of low BMD than females for all three outcomes (26%-32% vs. 18%-21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment-related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN-BMD site. CONCLUSION: Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow-up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.

QTc intervals at rest and during exercise assessed by group correction formulas in survivors of childhood acute lymphoblastic leukemia.

INTRODUCTION: Early signs of subclinical cardiac damage must be identified before they turn into clinical manifestations. Tailoring a formula is relevant for precise QTc evaluation in childhood acute lymphoblastic leukemia (ALL) survivors considering they are at risk of long-term cardiac problems. Therefore, we aim to develop group heart rate correction formulas for QT intervals in childhood ALL survivors at rest and during exercise, and to assess the applicability of these methods across a variety of risk groups exposed to diverse chemotherapy dosages. METHODS: Two hundred and fifty childhood ALL survivors in the PETALE study were classified into 3 groups depending on their prognostic risk group. ECG measurements (QT and RR intervals) were made at rest and during a cardiopulmonary exercise test. QT correction for heart rate was applied using 5 different formulas, which included 2 previously published formulas and 3 group-specific formulas for each sex. RESULTS: The QT/RR relation showed 2 different curves between rest and during exercise, which was worse for females. Group-specific QTc formulas allowed adequate heart rate-corrected QT interval, independently of the cumulative dose of doxorubicin received during treatment. Group-specific formulas showed significantly shorter QTc intervals than QTc from Bazett's formula. QTc (Bazett's formula) values surpassed the established clinical norm in 22 males (11%) and 22 females (11%), with a majority occurring during exercise, affecting 15 males (7.5%) and 10 females (5%). CONCLUSION: This study shows the applicability of personalized group correction of QT/RR data in childhood ALL survivors. Our comprehensive assessments (spanning rest, exercise, and recovery) is an effective approach for risk stratification of cardiac complications in childhood ALL survivors.

Feasibility Study of Taking Back Control Together, an Intervention to Support Parents of Children with Cancer.

INTRODUCTION: Parents of children with cancer can experience increased emotional distress. This study aimed to assess the feasibility (i.e., reach, treatment fidelity, and social validity) of Taking Back Control Together (TBCT). METHODS: We assessed reach with the enrollment and dropout ratios. We assessed treatment fidelity using items from existing programs, controlling for the reliability of the items. For social validity, we used an adapted version of the Treatment Evaluation Inventory and compared means with theoretical cut-points. RESULTS: 42 participants enrolled in the intervention. The enrollment and dropout ratios were 39% and 38%, respectively. Treatment fidelity was 77.3-84.3% (95%CI 75.3-86%). Acceptability (M = 90%), satisfaction (M = 87%), and relevance (M = 82%) were significantly positive. CONCLUSION: This study suggests that certain elements of TBCT need to be reassessed before the intervention is pilot tested. Although reach was likely impacted by the COVID-19 pandemic, it could be improved with some modifications to the intervention.

Cardiopulmonary response to exercise in adults born very preterm.

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O2 consumption (peak VO2) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg-1 lean body mass·min-1) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO2 to work-rate relationship (ΔVO2/ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO2) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO2Results suggest limitations with peripheral O2 uptake in the muscle with reduced ΔVO2/ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O2 use during exercise are warranted to better understand mechanisms of exercise limitation.

Do problem-solving skills help mitigate emotional distress through perceived control and self-efficacy in parents of children with cancer?

INTRODUCTION: Parents of children with cancer face psychological challenges that can result in significant distress. It has been found that problem-solving (PS) could mitigate emotional distress (ED) in this population, but mechanisms of this relation are poorly understood. This study aimed to assess whether there is a link between PS and ED through perceived control and self-efficacy. METHODS: We included 119 parents (67 mothers, 52 fathers, including 50 couples) whose child was diagnosed with cancer. We evaluated whether PS was associated with ED through perceived control and self-efficacy in couples of parents. RESULTS: We found no direct association between PS and ED (ß = -0.01, p = 0.92). Our results indicated a significant indirect effect between ED and PS with perceived control as the intermediary variable (ß = -0.24, p < 0.001, 95% CI [-0.41, -0.11]). However, there was no indirect association between ED and PS with self-efficacy as the intermediary variable (ß = -0.04, p = 0.26, 95% CI [-0.11, 0.09]). The effect size was large in magnitude (R2  = 0.59 for ED). CONCLUSION: The mitigating role of PS on ED is better explained by an enhanced experience of control than by improved self-efficacy. Future interventions should directly target the action mechanism behind PS and ED in both mothers and fathers by targeting their perceived control.

Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments.

INTRODUCTION: Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors' heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function. METHODS: A total of 196 childhood ALL survivors were stratified (standard risk [SR], high risk with and without dexrazoxane (HR+DEX and HR). We performed a complete transthoracic echocardiographic assessment with M-mode echocardiography, Doppler, and Tissue Doppler. We used 2-dimensional and 3-dimensional echocardiography to measure the left ventricular ejection fraction, whereas myocardial strain imaging was used to obtain global strain indices. RESULTS: Although most cardiac and arterial dimension parameters were not different between groups, a difference was observed in posterior intima of the right carotid ( P =0.017). Diastolic functions analyses reported that LV shortening fraction and left and right ventricular lateral S' wave amplitudes were lower in HR than in SR and HR+DEX groups ( P =0.028, P =0.048, and P =0.005, respectively). The LV lateral E' in diastolic function was lower in the HR than in SR and HR+DEX groups ( P =0.036). The LV end-systolic wall stress was higher in HR than in SR and HR+DEX groups ( P =0.009). A decrease contractility was observed, while the effect was not group specific. Strain rate was not different between groups, as opposed to tissue Doppler measurements. CONCLUSIONS: This study showed that dexrazoxane treatments could limit subclinical cardiac dysfunction in childhood ALL survivors, whereas survivors in HR group who did not receive dexrazoxane had potential subclinical cardiac damage observable in heart failure patients. Echocardiographic screening for survivors must be part of the follow-up routine in cardio-oncology.

Cardiac Mechanical Performance Assessment at Different Levels of Exercise in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments. METHODS: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated. RESULTS: We observed significant differences between the different levels of exercise for both VAC ( P <0.0001) and CWE parameters ( P =0.001). No significant differences were reported between prognostic risk groups at rest and during the CPET. Nevertheless, we observed that survivors in the SR group had a VAC value slightly lower than heart rate (HR)+DEX and HR groups throughout the CPET. Moreover, survivors in the SR group had a CWE parameter slightly higher than HR+DEX and HR groups throughout the CPET. CONCLUSIONS: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.

Abnormal HDL lipid and protein composition following pediatric cancer treatment: an associative study.

BACKGROUND: Long-term childhood cancer survivors (CCS) are at high risk of having dyslipidemia including low high density lipoprotein cholesterol (HDL-C). However, little is known about the prevalence of low HDL-C and the impact of therapy exposure on HDL composition early after treatment is terminated. METHODS: This associative study included 50 children and adolescents who had completed their cancer treatments (< 4 years). Clinical characteristics (demographic, diagnosis, treatment, anthropometric parameters), fasting plasma lipids, apoliporoteins (Apo) A-I and composition of HDL fractions (HDL2 and HDL3) were assessed. Data were stratified according to the presence of dyslipidemia and median doses of therapeutic agents and compared using Fisher exact or Mann-Whitney tests. Univariate binary logistic regression analyses were carried out to evaluate the associations between the clinical and biochemical characteristics and having low HDL-C. Composition of HDL2 and HDL3 particles was assessed in a sub-group of 15 patients and compared to 15 age- and sex-matched healthy controls using Wilcoxon paired test. RESULTS: Of the 50 pediatric cancer patients included in this study (mean age: 11.30 ± 0.72 y; mean time since end of treatment: 1.47 ± 0.12 y; male: 38%), 8 had low HDL-C (16%), all of which were adolescent at diagnosis. Higher doses of doxorubicin were associated with lower HDL-C and Apo A-I levels. In hypertriglyceridemic patients and compared to normolipidemics, triglycerides (TG) content was greater in HDL2 and HDL3 fractions whereas esterified cholesterol (EC) content was lower in HDL2. Enrich TG content of HDL3 and lower EC of HDL2 was found in patients exposed to ≥ 90 mg/m2 doxorubicin. Factors positively associated with the risk of having low HDL-C were age, being overweight or obese and exposure to doxorubicin ≥ 90 mg/m2. Compared to healthy controls, a sub-group of 15 patients showed higher TG and free cholesterol (FC) content of HDL2 and HDL3 and lower EC content in HDL3. CONCLUSIONS: Overall, we found abnormalities in HDL-C and Apo A-I levels and in HDL composition early after pediatric cancer treatment that are influenced by age, overweight or obesity status and exposure to doxorubicin.

Substrate oxidation during exercise in childhood acute lymphoblastic leukemia survivors.

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity (%V̇O2peak) and was used to determine the MFO and the peak fat oxidation (Fatmax). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fatmax and crossover point were not different between the groups (p = .078; p = .765; p = .726). Fatmax and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) (p = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors' substrate oxidation.

Cardiometabolic Health After Pediatric Cancer Treatment: Adolescents Are More Affected than Children.

This cross-sectional study aimed at comparing the cardiometabolic (CM) health of children and adolescents and identifying factors associated with CM complications shortly after cancer treatment. Cancer-related characteristics, blood pressure (BP), anthropometry, and biochemical parameters were collected in 80 patients (56.3% female, mean age: 11.8 years; range: 4.5 - 21.0) a mean of 1.4 years following therapy completion. Compared to children, adolescents had higher mean z-score of insulin (-0.47 vs. 0.20; P = 0.01), HOMA-IR (-0.40 vs. 0.25; P = 0.02), waist-to-height ratio (0.36 vs. 0.84; P = 0.01), subscapular skinfold thickness (-0.19 vs. 0.47; P = 0.02), total body fat (-1.43 vs. 0.26; P < 0.01), and lower mean z-score of HDL-C (0.07 vs. -0.53; P < 0.01). Adolescents were more likely to have high BP (42% vs. 15%; P < 0.01), dyslipidemia (64% vs. 15%; P < 0.001), and cumulating ≥ 2 CM complications (42% vs. 2%; P < 0.001) than children. Adiposity indices (z-scores) were associated with high BP [odds ratio (OR) ranging from 2.11 to 4.09] and dyslipidemia (OR ranging from 2.06 to 4.34). These results suggest that adolescents have a worse CM profile than children shortly after therapy and that adiposity parameters are associated with CM complications, highliting the importance to develop intervention strategies targeting this population.

The impact of cancer on theory of planned behavior measures and physical activity levels during the first weeks following cancer diagnosis in children.

BACKGROUND: The theory of planned behavior (TPB) is used to document children's health behaviors linked to their physical activity. The TPB model and its components have been applied to comprehend the adoption of physical activity along informational and motivational parameters. Thus, this exploratory study aims to assess the evolution of children's physical activity levels (MVLPA) during the first weeks of their cancer, in addition to documenting the evolution of the TPB measures, self-reported fitness, and self-esteem in the physical domain to better understand children's physical activity behavior. METHODS: A total of 16 children (8 boys and 8 girls) with cancer answered psychosocial questionnaires at the diagnosis of cancer (time 1) and at 6 to 8 weeks (time 2) to assess the TPB measures, self-reported fitness, self-esteem in the physical domain, and their daily physical activities. RESULTS: A significant decrease of 41.2 min/days of daily MVLPA was observed between the time at cancer diagnosis (50.5 ± 32.8 min/days) and 6 to 8 weeks after the first interview (9.3 ± 9.1 min/days). We found that the time after the diagnosis of cancer negatively impacted children's TPB measures (mean in attitude, injunctive norms, identity, facilitating factors, self-confidence, and intention) and MVLPA levels. The TPB model explains 40% of the variance in MVLPA by the injunctive norms during the first weeks following cancer diagnosis in children. CONCLUSION: The findings of this study highlight the negative impacts of cancer on children's TPB measures, self-reported fitness, and self-esteem in the physical domain and self-reported MVLPA levels over 4 to 6 weeks following the diagnosis. These findings help to better understand the effect of cancer diagnosis on children's physical activity behavior.

Maximal cardiopulmonary exercise testing in childhood acute lymphoblastic leukemia survivors exposed to chemotherapy.

PURPOSE: The purpose of this study was to demonstrate if childhood acute lymphoblastic leukemia (ALL) survivors exposed to chemotherapy (i.e., doxorubicin) are able to achieve a safe maximal cardiopulmonary exercise test (CPET). METHODS: A total of 250 childhood ALL survivors were eligible to undergo a CPET on ergocycle. Analyses were performed in 216 survivors and stratified in regard to their prognostic risk groups: 99 survivors (55 males and 44 females) at standard risk and 117 survivors (56 males and 61 females) at high risk. RESULTS: Results showed that 100% (n = 216) of survivors completed a maximal CPET confirmed by the achievement of two out of three of the following criteria: 197 survivors (91.2%) reached a peak RER value of ≥ 1.15, 197 survivors (91.2%) reached a RPE score > 7, and 210 survivors (97.2%) reached a maximal heart rate ≥ 85% of the predicted value. Linear regression analysis showed a significant association between the survivors' cumulative dose of doxorubicin and their VO2 peak measured. Two non-fatal adverse events were observed and reported at the end of the maximal CPET, while non-fatal adverse events were reported in 5 survivors during the recovery period. None of these events resulted in a long-term complication. CONCLUSION: Childhood ALL survivors with prior exposure to chemotherapy can achieve a safe maximal CPET. They were able of achieving a maximal exercise test without being limited by symptoms, potential overprotection, or musculoskeletal issues. Thus, it should be the norm to realize a CPET prior a physical activity program to propose an optimal prescription. This study provides important information regarding the maximal physiological parameters that childhood ALL survivors are able to reach and have important clinical implications in the exercise and oncology field for this population of survivors.

Validity and reliability of the French version of the Pediatric Quality of Life Inventory™ brain tumor module.

INTRODUCTION: Assessing health-related quality of life (HRQoL) is an increasingly important aspect of standard care in pediatric oncology. Currently, there is a gap in the availability of French questionnaires to assess the quality of life of French-speaking pediatric brain tumor (PBT) patients, which has important implications in the care of this population. The first aim of this study was to translate the original English Pediatric Quality of Life Inventory™ (PedsQL) brain tumor module version into French. The second aim was to describe the stability, repeatability and convergent validity of the French PedsQL brain tumor module. METHODS: A total of 61 PBT patients were included in this study. Among them, 15 children and 20 parents participated in the translation process. As part of the validation study, 48 children and 48 parents answered the PedsQL brain tumor module twice, and the PedsQL generic core scales and the patient-reported outcomes measurement information system (PROMIS-37 pediatric profile v2.0) questionnaire were administered once to the participants. The mean age of the 25 boys and 23 girls was 8.3 ± 4.8 years. For temporal stability, we used intraclass correlation coefficients (ICCs), for repeatability, we used the Bland and Altman method to assess the accuracy at a 1-week interval, and we used Pearson's correlation coefficients for convergent validity between the PedsQL brain tumor module, PedsQL general module and the PROMIS. RESULTS: Temporal stability for the parent proxy-reports (average ICC = 0.98) and the child self-reports (average ICC = 0.98) were excellent. There was a high absolute stability over a 1-week interval for the parent proxy-reports (ICC > 0.96) and child self-reports (ICC > 0.96). Convergent validity between parent proxy-reports and child self-reports was supported by positive correlations for five subscales. Children reported higher scores in cognitive problems and the movement and balance parameters than their parents and reported lower scores on the worry parameter than their parents. CONCLUSION: The strong psychometric properties of the French version of the PedsQL brain tumor module indicate that it is a validate and reliable questionnaire to measure HRQoL in PBT patients. The availability of a French version of the PedsQL brain tumor module supports the wider dissemination of the assessment of HRQOL in PBT patients.

Heart rate response and chronotropic incompetence during cardiopulmonary exercise testing in childhood acute lymphoblastic leukemia survivors.

Cardiopulmonary exercise tests (CPET) focusing on analyses of heart rate (HR) responses and chronotropic incompetence (CI) could provide early information about treatment's negative cardiac effects. We examined childhood acute lymphoblastic leukemia (ALL) survivors' HR response during maximal CPET and identified survivors with CI. A total of 250 childhood ALL survivors underwent a CPET on ergocycle to assess their HR response. We used a multiparametric structure of three methods to assess survivors' CI, as follows: 1) age-predicted HRmax (APMHR): failure to achieve 85% of the APMHR at the peak of CPET; 2) HR reserve (HRR): failure to achieve 80% of the HRR at the peak of CPET; and 3) metabolic chronotropic relationship (MCR): failure to reach an MCR slope ratio >0.8 at each stage of the CPET. Among 250 childhood ALL survivors, 216 survivors performed a maximum CPET. We observed that 73 males and 74 females did not achieve their predicted HRmax. We found that 6 survivors did not achieve 85% of their APMHR (80.9 ± 3.9%) and had an MCR below 80% (53.9 ± 13.8%). In addition, 16 survivors did not achieve 80% of their HRR (71.0 ± 7.4%) and among them, 15 survivors had an MCR below 80% (61.0 ± 12.1%). Survivors with CI had a significantly lower cardiorespiratory fitness than those without CI. This study shows that survivors are at risk of developing altered HR responses and CI many years after the end of their cancer treatments. These findings highlight the importance of early detection of cardiac damage due to cancer treatments.

Physical Activity and Sedentary Behaviors in Childhood Acute Lymphoblastic Leukemia Survivors.

INTRODUCTION: More than two thirds of survivors have long-term adverse effects, and no study proposes a portrait of physical activity level in childhood acute lymphoblastic leukemia survivors. The aims of this study were to present the cardiorespiratory fitness (CRF) levels of survivors detailed overview sedentary activities portrait. METHODS: A total of 247 childhood acute lymphoblastic leukemia survivors were included in our study. Survivors underwent a cardiopulmonary exercise test on ergocycle and completed physical activity and sedentary questionnaires to assess their leisure physical and sedentary activities and total daily energy expenditure. RESULTS: Up to 67% of survivors (84% below 18 y and 60% 18 y of age or above) did not fulfill the physical activity guidelines. Their CRF was reduced by almost 16% in regard to their predicted maximum oxygen consumption (VO2peak). Almost three quarters of the survivors (70% below 18 y and 76% 18 y of age or above) spent >2 hours/day in leisure sedentary activities. Adult survivors who received high doses of anthracyclines and those who received radiation therapy had decreased odds to spend ≥2 hours/day in sedentary activities. CONCLUSIONS: Our results showed that survivors, especially children, were not active enough and had a reduced CRF. This study highlights the importance of promoting physical activity in survivors, especially because they are exposed to an increased risk of chronic health problems, which could be mitigated by physical activity.

The VIE study: feasibility of a physical activity intervention in a multidisciplinary program in children with cancer.

BACKGROUND: Cancer is one of the leading causes of death in the world. The physiological and psychological benefits of physical activity have been shown in children with cancer. However, almost one in two cancer patients do not follow the physical activity guidelines. The aim of this study will be to assess the feasibility of a physical activity program intervention in pediatric oncology and to assess the barriers and facilitators to the success or failure of this physical activity program. METHODS: The VIE (valorization, implication, and education) intervention is a multidisciplinary program including physical activity, nutritional, and psychological interventions in pediatric oncology. This study involves one intervention group that will be followed over 2 years (evaluations and physical activity interventions) and one control group that will participate in only one evaluation. Children from the intervention group have been diagnosed and will be undergoing treatment at the Charles-Bruneau oncology center from the Sainte-Justine University Health Center (Montreal, Canada). The feasibility of this program will be measured through a comparison between sessions performed and sessions scheduled, while the security will be measured according to the number of reported incidents. DISCUSSION: This study will examine the effects of exercise in pediatric oncology from diagnosis to the expected end of treatment (i.e., 2 years of follow-up). Currently, there are only a few longitudinal studies on physical activity and pediatric cancer. Physiological and psychological tests will allow a better knowledge of the evolution of the physical fitness and mental health of the patients during the period of care. It is necessary to document and provide complementary knowledge in the pediatric oncology field in order to engage the discourse with pediatric oncology health professionals to help patients during and after treatment. This is an important study in the exercise and oncology field to help patients and their family during and after cancer treatments.

Observations on changes in ventricular repolarization following four weeks of exercise training in chronic heart failure patients.

OBJECTIVE: The aim of this study was to investigate the effects of exercise training on ventricular repolarization dynamicity and heart rate variability in chronic heart failure patients. DESIGN: A total of 22 chronic heart failure patients with reduced ejection fraction in sinus rhythm were included in the study. The patients were in NYHA classes II-III with an ejection fraction of 29.7 ± 7.7%. Before and after 4 weeks of aerobic exercise training, all patients performed a cardiopulmonary exercise test, a standard twelve-lead electrocardiogram and a 24 h Holter recording from which heart rate variability and ventricular repolarization dynamicity were assessed. RESULTS: We observed a significant decrease of QTpeak (p < .001) and QTend (p < .001) at RR intervals ranging from 600 to 1000 ms on 24 h QT/RR regressions after 4 weeks of exercise training. Our analyses revealed that short-term exercise training induced significant changes in the frequency and time domain HRV parameters on an overall time-period of 24 h. CONCLUSION: Four weeks of exercise training induced significant changes in ventricular repolarization dynamicity in chronic heart failure patients. In addition, short-term exercise training was enough to improve patients' heart rate variability.

The effect of cardiorespiratory fitness and physical activity levels on cognitive functions in survivors of childhood acute lymphoblastic leukemia.

Introduction. Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of the treatment. Regular physical activity and a good cardiorespiratory fitness can decrease the risks of neurological disturbances and increase cognitive function scores. The aim of this study was to examine the effect of good cardiorespiratory fitness and physical activity levels on cognitive functions.Methods. We enrolled 219 survivors of childhood ALL. The participants underwent a cardiopulmonary exercise test, neuropsychological tests of executive functions (i.e. verbal fluency, cognitive flexibility, working memory, processing speed) and completed a physical activity questionnaire. We calculated the odds ratio to obtain the preventive fraction of physical activity and cardiorespiratory fitness levels on cognitive functions.Results. The cohort is 52% male and 48% female. A total of 182 survivors (83%) have a cardiorespiratory fitness below their predicted (<100%). Our analyses show that there is an association between good cardiorespiratory fitness and processing speed (preventive fraction of 70% for dominant hand (p < 0.01) and 65% for non-dominant hand (p < 0.01)) and with cognitive flexibility identified as the category switching measure of the D-KEFS verbal fluency (preventive fraction of 61%; p < 0.05).Conclusion. Good cardiorespiratory fitness and good levels of physical activity were associated to a preventive fraction for most cognitive function parameters measured. Good cardiorespiratory fitness levels were significantly associated with a lower prevalence of deficits in processing speed (i.e., dominant hand and non-dominant hand) and in cognitive flexibility (i.e., category switching) in childhood acute lymphoblastic leukemia survivors.

Identification of genetic association between cardiorespiratory fitness and the trainability genes in childhood acute lymphoblastic leukemia survivors.

BACKGROUND: The progress of treatments of childhood acute lymphoblastic leukemia (ALL) has made it possible to reach a survival rate superior to 80%. However, the treatments lead to several long-term adverse effects, including cardiac toxicity. Although studies have reported associations between genetic variants and cardiorespiratory fitness, none has been performed on childhood ALL survivors. METHODS: We performed whole-exome sequencing in 239 childhood ALL survivors from the PETALE cohort. Germline variants (both common and rare) in selected set of genes (N = 238) were analyzed for an association with cardiorespiratory fitness. RESULTS: Our results showed that the common variant in the TTN gene was significantly associated with a low cardiorespiratory fitness level (p = 0.0005) and that the LEPR, IGFBPI and ENO3 genes were significantly associated with a low cardiorespiratory fitness level in female survivors (p ≤ 0.002). Also, we detected an association between the low cardiorespiratory fitness level in participants that were stratified to the "high risk" prognostic group and functionally predicted rare variants in the SLC22A16 gene (p = 0.001). Positive associations between cardiorespiratory fitness level and trainability genes were mainly observed in females. CONCLUSIONS: For the first time, we observed that low cardiorespiratory fitness in childhood ALL survivors can be associated with variants in genes related to subjects' trainability. These findings could allow better childhood ALL patient follow-up tailored to their genetic profile and cardiorespiratory fitness, which could help reduce at least some of the burden of long-term adverse effects of treatments.

Prevention of Long-term Adverse Health Outcomes With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of therapy. A regular practice of physical activity and a good cardiorespiratory fitness have the potential to reduce the risk of chronic disease and improve quality of life. The aim of this study was to evaluate in a cohort of ALL survivors, the association between a good cardiorespiratory fitness or the respect of physical activity guidelines and major long-term health outcomes. METHODS: In total, 247 ALL survivors underwent a cardiopulmonary exercise test, completed a physical activity questionnaire and a battery of clinical examinations. We calculated the odds ratio to obtain the preventive fraction (PF) to evaluate the effects of the cardiorespiratory fitness and physical activity levels on health outcomes (ie, obesity, metabolic health, cardiac health, cognitive health and mood, bone health). RESULTS: Despite their young age, 88% of the participants presented at least one adverse health outcome, and 46% presented ≥3. Their cardiorespiratory fitness was also lower than expected with a median VO2 peak reaching 84% of the predicted value. In the analyses using cardiorespiratory fitness, statistically significant PFs were observed for obesity (0.30), low-high-density lipoprotein-cholesterol (0.21) and depression (0.26). In the physical activity level analyses, statistically significant PFs were observed for obesity, depression, and low bone mineral density, with a PF of 0.55, 0.81, and 0.60, respectively. CONCLUSIONS: Our results indicate that a good cardiorespiratory fitness and physical activity level induced a preventive action for most health outcomes studied and was associated with a lower late adverse effects prevalence in ALL survivors.