Inhospital Exercise Training in Children With Cancer: Does It Work for All?

Purpose: Physical exercise training might counteract the weakening effects of both pediatric cancer and anti-cancer treatment. We aimed to analyze the prevalence of "responders" and "non-responders" to inhospital exercise training in children with cancer and to identify the factors that could influence responsiveness, which might help personalize exercise interventions for this patient population. Methods: We performed an ancillary analysis of the randomized controlled trial "Physical activity in Pediatric Cancer" (NCT01645436), in which 49 children with solid tumors were allocated to an inhospital exercise intervention or control group. The present study focused on the children in the former group (n = 24, 10 ± 4 years), who performed 3 weekly training sessions (aerobic + strength exercises). The intervention lasted 19 ± 8 weeks (i.e., from the start to the end of neoadjuvant chemotherapy treatment). A responder-vs-non-responder analysis was performed for physical capacity-related endpoints (five-repetition maximum strength, functional mobility tests, and cardiorespiratory fitness [CRF]). Only those participants showing improvements in a given test of a magnitude greater than both the random error and the threshold for clinically meaningful changes were considered responders. Results: Most participants improved their performance in the strength tests, with 80, 88, and 93% of total showing a positive response for seated bench press, lateral row, and leg press, respectively (p < 0.001). No significant improvements were observed for the functional mobility tests or CRF (p > 0.05, rate of responsiveness ≤ 50%). No differences between responders and non-responders were observed for sex, age, type of cancer, or treatment (i.e., including or not anthracyclines/radiotherapy). However, significant differences (p < 0.05) were observed between responders and non-responders for baseline performance in all the tests, and a significant (p < 0.05) inverse relationship was found between baseline performance and relative improvement for most endpoints. Conclusions: Although most children improved their muscle strength after the exercise intervention, a considerable individual variability was observed for the training responsiveness of functional mobility and CRF. A lower baseline performance was associated with a higher responsiveness for all the study endpoints, with the fittest children at the start of treatment showing the lowest responses. Efforts to individualize exercise prescription are needed to maximize responsiveness in pediatric cancer patients.

Effects of Exercise on the Immune Function of Pediatric Patients With Solid Tumors: Insights From the PAPEC Randomized Trial.

The purpose of this study was to assess the effects of an in-hospital exercise intervention during neoadjuvant chemotherapy on the inflammatory profile and immune cell subpopulation in 20 children with solid tumors (control [n = 11] and exercise group [n = 9]). Although no significant interaction (group × time) effect was found with an analysis of variance test, we found a trend toward an interaction effect for natural killer cells expressing the immunoglobulin-like receptor KIR2DS4, with their numbers remaining stable in the exercise group but increasing in controls. Our data support that exercise interventions are safe in pediatric cancer patients with solid tumors during chemotherapy treatment despite its aggressive, immunosuppressive nature.

Exercise Intervention in Pediatric Patients with Solid Tumors: The Physical Activity in Pediatric Cancer Trial.

INTRODUCTION: The randomized controlled trial "Physical Activity in Pediatric Cancer" determined the effects of an inhospital exercise intervention combining aerobic and muscle strength training on pediatric cancer patients with solid tumors undergoing neoadjuvant chemotherapy. METHODS: Participants were allocated to an exercise (n = 24, 17 boys; mean ± SEM age, 10 ± 1 yr) or control group (n = 25, 18 boys; 11 ± 1 yr). Training included three sessions per week for 19 ± 2 wk. Participants were assessed at treatment initiation, termination, and 2 months after end treatment. The primary endpoint was muscle strength (as assessed by upper and lower-body five-repetition-maximum tests). Secondary endpoints included cardiorespiratory fitness, functional capacity during daily life activities, physical activity, body mass and body mass index, and quality of life. RESULTS: Most sessions were performed in the hospital's gymnasium. Adherence to the program averaged 68% ± 4% and no major adverse events or health issues were noted. A significant interaction (group-time) effect was found for all five-repetition maximum tests (leg/bench press and lateral row; all P < 0.001). Performance significantly increased after training (leg press: 40% [95% confidence interval [CI], 15-41 kg); bench press: 24% [95% CI, 6-14 kg]; lateral row 25% [95% CI, 6-15 kg]), whereas an opposite trend was found in controls. Two-month post values tended to be higher than baseline for leg (P = 0.017) and bench press (P = 0.014). In contrast, no significant interaction effect was found for any of the secondary endpoints. CONCLUSION: An inhospital exercise program for pediatric cancer patients with solid tumors undergoing neoadjuvant treatment increases muscle strength despite the aggressiveness of such therapy.

Valoración de la capacidad funcional de niños con tumores sólidos / Assessment of the exercise capacity of children with solid tumors

Introducción: El ejercicio físico podría ser una herramienta eficaz para mantener alta la capacidad funcional en los pacientes con tumores sólidos (TS), pero antes de comenzar a analizar su efecto, debemos establecer si dicha capacidad funcional está disminuida en la población que padece esta enfermedad. El objetivo de este trabajo fue comparar la capacidad funcional y la agilidad de las tareas de la vida diaria en niños que padecen TS respecto a niños sanos controles (NS). Material/métodos: Se seleccionaron 52 niños, 24 pacientes de TS del HIUNJ (edad (años) 10±4,2; altura (cm) 146±21,9; peso (kg) 41,3±20,2; IMC (kg/m2) 18,1±4,9) y 28 niños sanos pareados en edad(años) 8 ±3,4; altura (cm) 137±21,4; peso (kg) 33,6±13,7; IMC (kg/m2) 17,1±2,1. Las variables analizadas fueron: capacidad funcional (VO2pico, VO2VT1) medida a través de prueba de esfuerzo con análisis de gases y agilidad (tiempo utilizado en los test funcionales «Test Up and Go 3m» (TUG-3) y «Test Up and Down Stairs12» (TUDS-12). Para el análisis de datos, se utilizó la prueba estadística T-student (SPSS.20). Resultados: La capacidad funcional, medida a través de VO2pico, en niños con TS fue significativamente más baja que en NS (25±8,8 ml·kg-1·min-1 vs 40,9±8,9 ml·kg-1·min-1 respectivamente), el VO2VT1 fue también menor para el grupo de niños de TS (17,1±6 ml·kg-1·min-1 vs 25,7±4,9 ml·kg-1·min-1). No se encontraron diferencias significativas en la FCpico. Los test funcionales no mostraron diferencias entre ambos grupos. Discusión/Conclusión: Los niños que padecen TS tienen un descenso de un 38,8% en su capacidad funcional. Según Myers et al. 2002 (N Engl J Med 2002; 4:793-801), un descenso de 3,5 ml/kg/min de la capacidad funcional se asocia con una reducción de un 12% en la tasa de longevidad en poblaciones enfermas. La capacidad funcional más baja de los niños con TS afecta al proceso evolutivo de su enfermedad, sugiriendo el ejercicio como herramienta capaz de incrementar dicha capacidad funcional

Introduction: Physical exercise would be an efficient tool in order to maintain a high exercise capacity in solid tumors patients (ST), but before to analyze its effects, we must establish whether this exercise capacity is reduced in the population who suffer this illness. The aim of this study was to assess and compare the exercise capacity and agility (functional mobility) of the day live tasks in children who suffer TS respect those healthy matched (HC). Materials and methods: We studied a total of 52 children, 24 patients of ST from HIUNJ (age (years old) 10±4,2; height (cm) 146±21,9; weight (kg) 41,3±20,2; BMI (kg/m2) 18,1±4,9) and 28 healthy control children matched in age (years old) 8 ±3,4; height (cm) 137±21,4; weight (kg) 33,6±13,7; BMI (kg/m2) 17,1±2,1. The studied outcomes included: exercise capacity (VO2peak, VO2VT1) measured by a treadmill exercise testing using a metabolic chart «breath by breath»; and agility or functional mobility (seconds), time to finish the «Test Up and Go 3m» (TUG-3) and «Test Up and Down Stairs 12» (TUDS-12). T-student (SPSS.20) statistical test was used to data analysis. Results: Exercise capacity, measured by VO2peak, was significantly lower in children with ST than in HC (25±8,8 ml·kg-1·min-1 vs 40,9±8,9 ml·kg-1·min-1 respectively) and the VO2VT1 was also lower in ST group (17,1±6 ml·kg-1·min-1 vs 25,7±4,9 ml·kg-1·min-1). We did not found significantly differences in the peak heart rate neither in the agility or functional mobility between both groups. Conclusions: Solid tumors children have a 38,8% reduced their exercise capacity. According to Myers et al. 2002 (N Engl JMed 2002; 4:793-801), an exercise capacity decrease of 3,5 ml·kg-1·min-1 is associated with a risk of longevity reduction of a 12%. A lower exercise capacity in the ST group concerns the illness evolutionary process, and they suggest the exercise as a tool be capable to increase this capacity

Physical Activity in Pediatric Cancer patients with solid tumors (PAPEC): trial rationale and design.

BACKGROUND: This randomized controlled trial on Physical Activity in Pediatric Cancer (PAPEC) was designed to assess the impact of an exercise program on pediatric cancer patients undergoing chemotherapy for solid tumors. METHODS AND DESIGN: 60 pediatric patients of both sexes, aged 4 to 18 years and undergoing treatment for extracranial primary solid tumors will be recruited for this trial. Each participant will be randomly assigned (with blocking on sex) to either an intervention or control (normal care) group. The intervention group will participate in combined inpatient physical training (aerobic + strength) for the duration of neoadjuvant chemotherapy. The intervention will include 3 weekly 60-70 min exercise sessions in the child's room or in a pediatric gym at the hospital, depending on the child's health state. In both groups, determination of several primary (cardio-respiratory fitness, muscle strength, functional capacity, physical activity levels, body weight and quality of life) and secondary outcomes [immune function and inflammatory profile (blood levels of 47 cytokines)] will be made at the following time points: (i) before the exercise intervention (immediately after diagnosis and before treatment onset); (ii) after the exercise intervention (upon termination of neoadjuvant chemotherapy); and (iii) after a detraining period (2 months after the intervention). DISCUSSION: The PAPEC trial will provide relevant new information on biological mechanisms and inform on the potential clinical use of exercise during pediatric cancer treatment as a simple way to prevent future long-term treatment effects and improve the general health state of pediatric cancer patients.

Treatment of cutaneous leishmaniasis with a topical antileishmanial drug (WR279396): phase 2 pilot study.

We studied the efficacy of WR279396, a topical formulation of aminoglycosides that cures 100% of cutaneous leishmaniasis lesions in mice. We conducted what is to our knowledge the first controlled study of WR279396 therapy for clinical cutaneous leishmaniasis. A total of 45 Colombian soldiers, all men, were randomly assigned to treatment with WR279396 (33 patients) or placebo (12 patients). Each lesion was treated twice daily for 20 days. Lesions were measured at the end of therapy and at 45, 90, and 180 days after treatment began. A total of 17 (61%) of 28 assessable WR279396-treated patients were cured, and 5 (55%) of 9 assessable placebo-treated patients were cured (P = 0.9). For the 36 lesions treated with WR279396 that were cured, cure took a mean of 35 days, whereas for the 6 lesions that were cured in the group of patients receiving placebo, cure time took a mean of 56 days (P = 0.04). WR279396 is a nontoxic topical formulation that significantly accelerated cure time in patients with Leishmania panamensis cutaneous leishmaniasis.