Real World Pediatric Oncology Rehabilitation in Italy ( ReWori )

Real World Pediatric Oncology Rehabilitation in Italy (ReWori) Study Protocol: Prognostic Factors of Functional Abilities in Children, Adolescents and Young Adults With Cancer Undergoing Rehabilitation

This observational study aims to describe changes in the functional abilities of children, adolescents and young adults with cancer who are undergoing physiotherapy or neuropsychomotor rehabilitation. This is real-world study aiming to describe normal rehabilitation pathways in many different hospitals or rehabilitation centres in Italy.

The primary research question is:

1) What are the longitudinal changes in functional abilities among these patients receiving physiotherapy or neuropsychomotor rehabilitation?

The secondary research questions are:

1. What types of rehabilitation practices are implemented across AIEOP centres?
2. What are the rehabilitation needs among patients undergoing physiotherapy or neuropsychomotor rehabilitation?
3. How does health-related quality of life differ across the various stages of the rehabilitation pathway? Participants undergoing usual rehabilitation treatment are evaluated on their functional abilities on a monthly basis. If they agree to participate in this study, the main characteristics of the rehabilitation treatment and the monthly evaluation are collected.

Each year in Italy, about 1,400 children, 800 adolescents are diagnosed with cancer, with survival rates approaching 80percent. Despite improved survival, cancer and its treatments often lead to functional impairments and delays in neuropsychomotor development, affecting the musculoskeletal, nervous, and cardiovascular systems. These limitations can occur throughout all phases of care, from diagnosis to post-treatment, making rehabilitation increasingly important to preserve and improve quality of life. Although rehabilitation is recognized as beneficial in paediatric oncology, current evidence on the effectiveness of physiotherapy and neuropsychomotor interventions remains limited. Research has largely focused on general physical activity rather than targeted rehabilitation aimed at restoring specific functions such as mobility, balance, or joint function. A 2021 Cochrane review highlighted the need for high-quality, multicentre studies with standardized protocols, homogeneous patient groups, clearly defined and measurable outcomes, and long-term follow-up.

Currently, there are no shared international guidelines or Core Outcome Sets (COS) for rehabilitation in paediatric oncology. To address this gap, the Italian Association of Paediatric Haematology and Oncology (AIEOP) developed consensus-based recommendations for rehabilitation assessment and treatment and promoted the validation of the Functional Abilities Assessment in Paediatric Oncology (FAAP-O) scale. However, there is still the lack of data on prognostic factors influencing functional outcomes, rehabilitation needs, and types of rehabilitation care provided to children, adolescents, and young adults with cancer.

The primary objective is to describe changes in functional abilities in patients undergoing physiotherapy or neuropsychomotor rehabilitation. Secondary objectives include describing rehabilitation practices across AIEOP centres, estimating rehabilitation needs, and assessing quality of life at different stages of rehabilitation. The main endpoint is represented by functional ability levels, which are measured using the FAAP-O scale for patients with all types of cancer except bone tumours, and the TESS-pTESS questionnaires for patients with bone tumours. Secondary endpoints include rehabilitation tools, rehabilitation goals, treatment intensity, types of exercises, incidence of rehabilitation referrals with related impairments, and quality of life measured using the PedsQL and Bt-DUX questionnaires. The study will be conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki. Ethical approval from local ethics committees is required before patient enrolment, and no external funding is provided for the study. Patient confidentiality will be ensured through anonymised data collection. Each participant will be assigned a centre specific alphanumeric code. Personal identifiers will be accessible only to the enrolling centre. The year of birth will be recorded to minimize data entry errors.

All participants, or their legal guardians, will receive detailed information about the study objectives, data handling, and confidentiality measures. Participation is voluntary and will not affect rehabilitation care. Written informed consent will be obtained prior to enrolment. Data analysis will include descriptive statistics for continuous and categorical variables. Changes in functional abilities over time will be evaluated using paired statistical tests, while mixed-effects regression models will be used to explore associations between predictors and outcomes in a multicentre, longitudinal framework. Statistical significance will be set at 5%. Based on the primary outcome measures (FAAP-O, pTESS, and TESS), a sample size of 199 participants is required to detect a small effect size (0.20) with 80% power. Accounting for an anticipated 20% dropout rate, the total enrolment target is 249 patients. A rehabilitation assessment will be carried out upon referral to the rehabilitation service and then on a monthly basis throughout the rehabilitation process. Data will be collected electronically using an online case report form (CRF) on the REDCap platform, accessible to all participating centres following the ethical committee approbation.

Inclusion Criteria:

• Diagnosis of cancer,
• Children, adolescents and young adults aged between 0 and 24 years old,
• Children, adolescents and young adults at any stage of treatment and off therapy,
• Children, adolescents and young adults referred to the Rehabilitation Service of AIEOP centres and Rehabilitation Centres that provide rehabilitation care for paediatric and young adult cancer patients involved in the study.

Exclusion Criteria:

• Failure to sign the consent/assent form for participation in the study by the subject and/or by the person exercising parental authority.