Abstract
BACKGROUND: Despite substantial advances in treatment, children and adolescents with cancer continue to face high morbidity and health issues, including cancer-related fatigue, treatment-related complications, and physical inactivity. Integrating exercise into pediatric oncology care has emerged as a promising approach to mitigate these burdens during cancer treatment. While preliminary data support its potential to reduce treatment-related side effects and enhance quality of life, robust evidence -especially from large, multicenter trials- remains limited. METHODS: The FORTEe trial is a randomized, controlled, multicenter trial evaluating a personalized and standardized exercise intervention powered to include 450 children, adolescents, and young adults undergoing cancer treatment across ten centers in Europe. The trial aims to provide high-quality evidence for integrating precision exercise therapy as part of standard care. Participants are randomly assigned to either the exercise intervention group, receiving a tailored, supervised 8-10 weeks lasting exercise program, or the control group, receiving usual care. The exercise program includes endurance, strength, flexibility, and balance training, adapted to each patient's age, fitness, and cancer treatment phase. Exercise sessions are intended to take place 3-5 times a week with moderate intensity, with both frequency and intensity adapted to the clinical condition of the individual. Digital tools and telehealth solutions support the intervention, allowing for both in-person and remote training. DISCUSSION: With a target enrolment of 450 patients, the FORTEe trial will be one of the largest interventional studies in pediatric exercise oncology. Given that childhood cancer is a rare disease, this sample size is only achievable through a multicenter approach. Enhancing statistical power, the large sample will enable more robust analyses of the intervention's effects in a diverse population across multiple European centers. CONCLUSION: As a progress beyond the current state-of-the-art, FORTEe has the ambition to implement pediatric exercise oncology as an evidence-based treatment option for all childhood cancer patients, ultimately integrating it as a standard into clinical practice worldwide. TRIAL REGISTRATION: The FORTEe trial was prospectively registered in the German Clinical Trials Register (DRKS00027978) on 28 January 2022 and on ClinicalTrials.gov (NCT05289739) on 21 March 2022.