Emma Jacobine Verwaaijen

Background: Consumer smartwatches offer potential for continuous monitoring of physical activity during childhood cancer treatment. However, their validity for measuring step count and heart rate in this population has not been established. Objective: This study examined the validity of a Withings smartwatch for monitoring step count and heart rate in children and adolescents undergoing cancer treatment. Methods: Children and adolescents aged 8 to 18 years under active cancer treatment wore a Withings smartwatch for 12 weeks. For validation purposes, children and adolescents simultaneously wore an ActiGraph wGT3X-BT accelerometer for 1 week under free-living conditions to assess step count agreement and were connected to a clinical heart rate monitor under resting conditions to assess heart rate agreement. Linear mixed models with participant ID as a random effect were used to estimate mean differences and derive 95% limits of agreement for repeated measurements. Results: A total of 14 children and adolescents participated in each of the validation analyses. The smartwatch recorded significantly fewer steps than the ActiGraph accelerometer for both steps per hour (mean difference 174 steps per hour; 95% limits of agreement=−283 to 633; P <.001) and steps per day (mean difference 3154 steps per day; 95% limits of agreement=−394 to 6702; P <.001), with increasing discrepancy at higher activity levels, suggesting proportional bias. No statistically significant difference in heart rate was observed between the smartwatch and the clinical heart rate monitor under resting conditions (mean difference −1.07 beats per minute; 95% limits of agreement=−17.55 to 15.41; P =.24). Conclusions: In children and adolescents undergoing cancer treatment, the Withings smartwatch showed minimal systematic bias for resting heart rate assessment, although individual variability was considerable. In contrast, step counts demonstrated systematic underestimation and wide limits of agreement compared with a research-grade accelerometer. The use of smartwatch-derived step counts for clinical benchmarking or goal setting in this population cannot currently be recommended.

Background: Children with cancer are at risk of reduced physical activity. Gaining insight into physical activity using smartwatches could improve understanding of individual potential during treatment, support early recognition of aberrant physical activity, and enable tailored support. Objective: This study aimed to explore the feasibility, barriers, facilitators, and considerations of long-term physical activity tracking using a smartwatch during childhood cancer treatment. Methods: In this prospective study, 30 children (age 8‐18 years) under active cancer treatment were included in 2 phases. During phase 1, 15 children wore a smartwatch daily for 12 consecutive weeks, and in-depth interviews were conducted to identify principal considerations used to optimize wearability and the methods for phase 2. In phase 2, another 15 children wore the smartwatch, and semistructured interviews were conducted at weeks 1, 3, 6, and 12. These interviews were thematically analyzed to identify barriers and facilitators. An iterative process of alternating data collection and analysis allowed for ongoing method refinement and deepening thematic analysis during the study period. Results: Key considerations for improvement identified in phase 1 led to refinements in phase 2, including enhanced engagement, regular prompts, customized plans, personalized setup, and improved aesthetics and comfort. The interviews conducted during phase 2 identified barriers and facilitators. The 4 most prominent themes were burden and resilience, motivational drivers and perception, insight and evaluation, and user experience and functionality. Feasibility was influenced by the child’s physical state and perceived burden. Motivation, perceived value, and expectations played crucial roles in sustaining adherence, while also the balance between positive reinforcement and potential confrontation affected long-term use. User experience, including attractiveness, comfort, and usability, impacted acceptance. Conclusions: Real-time and long-term physical activity tracking using a smartwatch in children during cancer treatment was not feasible in our cohort. A personalized approach, incorporating individual preferences and physical condition, is essential to support adherence.

Background: Cancer during pregnancy is a rare and significant life-changing event affecting approximately 1 in 1000-2000 pregnancies. With increasing maternal age and broader application of prenatal screening programs such as the Dutch Non-Invasive Prenatal Testing, incidental detection of maternal cancer is becoming more frequent. Advancements in safe treatment options during pregnancy, supported by the International Network on Cancer Infertility and Pregnancy (INCIP), have led to fewer pregnancy terminations. Consequently, more children are exposed to chemotherapy and other cancer treatments in utero. While short-term safety has been demonstrated for many oncological agents, long-term side effects including physical, neuromotor, neurocognitive, and psychosocial impacts on offspring and their families after delivery are still being assessed. Standard settings for surveillance and care of offspring and their families have, however, never been described. Objective: Given the importance of expertise in assessing the long-term outcomes of children, the Netherlands established the national centralized Cancer in Pregnancy (CIP) offspring outpatient clinic in 2018, which functions as a standard-of-care surveillance clinic and contributes data to the INCIP registry. Here we provide a demographic overview of referred families and to share (logistic) experiences with the national, centralized, multidisciplinary, and standardized long-term surveillance program for all Dutch children with in utero exposure to maternal cancer and its treatment. Methods: The CIP offspring outpatient clinic is located at the Princess Máxima Center for Pediatric Oncology and provides surveillance from infancy until 18 years of age. The, relatively small dedicated team, comprising pediatric oncologists, physiotherapists, and a psychological expert, offers a 1-day, multidisciplinary assessment, including physical examinations, neuromotor tests, cardiac monitoring (for anthracycline exposure), renal and auditory screening (for platinum agents), neurocognitive testing, and psychosocial evaluation. Surveillance is aligned with international INCIP guidelines. Results: From May 2018 to 2024, a total of 226 children (from 221 mothers) have been referred to the CIP offspring outpatient clinic, with 465 follow-up visits completed. The most common maternal cancer types were breast, gynecological, and hematological malignancies. Most women (58%) received chemotherapy during pregnancy; 11% of them had surgery only, 3% underwent radiotherapy, 3% underwent immunotherapy, 16% received a combination of treatment modalities, and 8% did not undergo treatment during pregnancy. Anthracyclines were the most commonly used agents. Median gestational age at delivery was 37.3 weeks. Fourteen percent of the mothers died shortly after delivery, underscoring the emotional and logistical challenges for families. Conclusions: The CIP offspring outpatient clinic provides a unique, structured approach to long-term surveillance for in utero–exposed children, which enables early detection of potential late effects and provides comprehensive family support. By sharing knowledge and experiences from the unique setting of this national centralized CIP offspring outpatient clinic, this initiative may inspire other countries in developing similar translational facilities to support affected families and improve care worldwide. International Registered Report Identifier (IRRID): DERR1-10.2196/71612

Introduction: Childhood cancer survivors have an increased risk of lifetime morbidity and mortality. To improve outcomes, the physical impact of treatment toxicity must be minimised in the acute phase. Using a framework to identify early signs of physical vulnerability could provide an avenue for early intervention. Yet, existing models of physical vulnerability (sarcopenia and frailty) are adult-based definitions and require adaptation as they do not reflect the unique pathophysiology of paediatric cancer. Using phenotypes of sarcopenia and frailty as base, this study aims to establish a consensus definition of the physically vulnerable child with cancer. Methods and analysis: A Delphi consensus approach is guided by a project team of four specialised oncology healthcare professionals. Five stages include defining the problem area, selecting panel members, conducting four Delphi rounds, establishing closing criteria and validation of results. A focus group of international experts will meet to define the problem area, in addition to a scoping review to collate existing definitions and assessments of sarcopenia and frailty within paediatric contexts. Delphi panel members will include multinational clinicians with >5 years’ experience in the acute paediatric setting, and researchers specialising in sarcopenia and/or frailty in paediatric cancer. Delphi rounds will aim to achieve consensus on how to define physical vulnerability in children with cancer. Consensus will be considered achieved when 80% or more of panellists agree. A series of focus groups with select members of the Delphi panel, and families, children, and adolescents affected by paediatric cancer will be held to validate results. Ethics and dissemination: The study has ethics approval through the Royal Children’s Hospital Human Ethics Committee (number 3707). Results from this study will be published in peer-reviewed academic journals and disseminated via scientific conference(s) and key stakeholders.

Background: A cancer diagnosis and its treatment often disrupt a child’s and adolescent’s normal level of physical activity, which plays a vital role in their development and health. They are therefore often less physically active during treatment than before the diagnosis or compared to healthy peers. Today, there is no comprehensive overview of the safety, feasibility, clinical effectiveness, and potentially long-lasting impact of physical activity (PA) interventions in this population. Methods: We conducted a systematic review in PubMed according to PRISMA guidelines to evaluate studies on PA interventions during cancer treatment in children and adolescents up to 25 years of age. We used the Joanna Briggs Institute’s critical appraisal tools to assess the risk of bias. Due to the heterogeneity in interventions and outcomes, we used descriptive approaches only to present the results. Results: Half of the 21 included studies were randomized controlled trials (10/21). PA interventions were found to be safe and feasible when tailored to the patient’s age, treatment phase, and clinical condition. Most studies reported improvements in physical fitness, strength, and quality of life, with some reductions in fatigue. Variability in interventions and outcomes, along with small sample sizes and heterogeneous patient populations, made it difficult to draw clear conclusions. Conclusions: PA appears to be a feasible and, in terms of injuries, safe adjunct to cancer treatment in children and adolescents. Despite promising trends, further large-scale, multicenter trials with standardized protocols are needed to better establish the long-term benefits and optimal interventions.

Purpose Acute lymphoblastic leukaemia (ALL) and its treatment cause side effects in paediatric patients which increase the risk of walking inability, limiting functional independence and quality of life. However, the incidence of walking inability, the time until onset and potential risk factors are unknown. Methods We retrospectively retrieved data in ALL patients (≤ 18 years). Walking inability was defined as the incompetence to walk independently from diagnosis until the end of early treatment. A Kaplan–Meier analysis was conducted to estimate the time until walking inability. To assess the effect of risk factors, we estimated a Cox regression model and performed a landmark analysis. Results In total, 226 patients (age median, 5.5 years; interquartile range, 3.4–11.7) were included. Walking inability was experienced by 15.0% at diagnosis and 28.3% during induction/consolidation1. Age at diagnosis (hazard ratio (HR) 0.901; 95% confidence interval (CI) 0.847–0.959) was a risk factor during induction/consolidation1. The landmark analysis at end of induction identified age at diagnosis (HR 0.898; 95% CI 0.830–0.971), delta weight-to-height Z-score (HR 0.577; 95% CI 0.410–0.812) and duration of hospitalizations (HR 1.076; 95% CI 1.005–1.152) as risk factors during consolidation1. Conclusion Fifteen percent experienced walking inability at diagnosis and 28.3% temporarily stopped walking during early treatment. This is concerning because walking inability leads to isolation and loss of independence. Patients with younger age, decreasing weight and longer hospitalizations during the first month of treatment were at highest risk. Informing patients and parents about the occurrence of walking inability and studies on physiotherapy and nutritional interventions are indicated.

BACKGROUND Cancer during pregnancy is a rare and significant life-changing event affecting approximately 1 in 1000-2000 pregnancies. With increasing maternal age and broader application of prenatal screening programs such as the Dutch Non-Invasive Prenatal Testing, incidental detection of maternal cancer is becoming more frequent. Advancements in safe treatment options during pregnancy, supported by the International Network on Cancer Infertility and Pregnancy (INCIP), have led to fewer pregnancy terminations. Consequently, more children are exposed to chemotherapy and other cancer treatments in utero. While short-term safety has been demonstrated for many oncological agents, long-term side effects including physical, neuromotor, neurocognitive, and psychosocial impacts on offspring and their families after delivery are still being assessed. Standard settings for surveillance and care of offspring and their families have, however, never been described. OBJECTIVE Given the importance of expertise in assessing the long-term outcomes of children, the Netherlands established the national centralized Cancer in Pregnancy (CIP) offspring outpatient clinic in 2018, which functions as a standard-of-care surveillance clinic and contributes data to the INCIP registry. Here we provide a demographic overview of referred families and to share (logistic) experiences with the national, centralized, multidisciplinary, and standardized long-term surveillance program for all Dutch children with in utero exposure to maternal cancer and its treatment. METHODS The CIP offspring outpatient clinic is located at the Princess Máxima Center for Pediatric Oncology and provides surveillance from infancy until 18 years of age. The, relatively small dedicated team, comprising pediatric oncologists, physiotherapists, and a psychological expert, offers a 1-day, multidisciplinary assessment, including physical examinations, neuromotor tests, cardiac monitoring (for anthracycline exposure), renal and auditory screening (for platinum agents), neurocognitive testing, and psychosocial evaluation. Surveillance is aligned with international INCIP guidelines. RESULTS From May 2018 to 2024, a total of 226 children (from 221 mothers) have been referred to the CIP offspring outpatient clinic, with 465 follow-up visits completed. The most common maternal cancer types were breast, gynecological, and hematological malignancies. Most women (58%) received chemotherapy during pregnancy; 11% of them had surgery only, 3% underwent radiotherapy, 3% underwent immunotherapy, 16% received a combination of treatment modalities, and 8% did not undergo treatment during pregnancy. Anthracyclines were the most commonly used agents. Median gestational age at delivery was 37.3 weeks. Fourteen percent of the mothers died shortly after delivery, underscoring the emotional and logistical challenges for families. CONCLUSIONS The CIP offspring outpatient clinic provides a unique, structured approach to long-term surveillance for in utero–exposed children, which enables early detection of potential late effects and provides comprehensive family support. By sharing knowledge and experiences from the unique setting of this national centralized CIP offspring outpatient clinic, this initiative may inspire other countries in developing similar translational facilities to support affected families and improve care worldwide. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/71612

The trajectory of hematopoietic stem cell transplantation (HSCT) is often accompanied by physically disabling complications that impair physical performance of pediatric patients. However, knowledge about when impairments in physical performance arise and the factors contributing to these impairments is limited. Therefore, we conducted a retrospective analysis of physical performance 100 days post-HSCT in patients aged 3–18 years. Additionally, we aim to elucidate the relationship between pre- and post-HSCT physical performance and to unravel the impact of intensive HSCT procedures on post-HSCT physical performance. To explore associations between physical performance outcomes post-HSCT and covariates, linear regression models were estimated. Seventy-seven patients were included with a median age of 11.8 years (interquartile range: 5.9, 14.8). Patients had lower hip flexion muscle strength and appendicular skeletal muscle mass and a slower rising from the floor time 100 days post-HSCT compared to average values of the normal population. Pre-HSCT physical performance was positively associated with physical performance post-HSCT, independent of age, the cumulative glucocorticoids dosage administered and the total duration of hospitalization during the HSCT trajectory. This explorative study highlights the potential role of prehabilitation in enhancing physical performance of pediatric HSCT patients.

Background: Dexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and functional abilities. The aim of this study was to establish the effect of a dexamethasone course on sarcopenia and physical frailty in children with ALL, and to explore prognostic factors.Methods: Patients with ALL aged 3–18 years were included during maintenance therapy. Patients had a sarcopenia/frailty assessment on the first day of (T1) and on the day after (T2) a 5‐day dexamethasone course. Sarcopenia was defined as low muscle strength in combination with low muscle mass. Prefrailty and frailty were defined as having two or ≥three of the following components, respectively: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity. Chi‐squared and paired t‐tests were used to assess differences between T1 and T2. Logistic regression models were estimated to explore patient‐ and therapy‐related prognostic factors for frailty on T2.Results: We included 105 patients, 61% were boys. Median age was 5.3 years (range: 3–18.8). At T1, sarcopenia, prefrailty, and frailty were observed in respectively 2.8%, 23.5%, and 4.2% of patients. At T2, the amount of patients with frailty had increased to 17.7% (p = 0.002), whereas the number of patients with sarcopenia and prefrailty remained similar. Higher ASMM (odds ratio [OR]: 0.49, 95% CI: 0.28–0.83), stronger handgrip strength (OR: 0.41, 95% CI: 0.22–0.77) and more physical activity minutes per day (OR: 0.98, 95% CI: 0.96–0.99) decreased the risk of frailty at T2. Slower walking performance (OR: 2, 95% CI: 1.2–3.39) increased the risk. Fatigue levels at T1 were not associated with frailty at T2.Conclusion: Physical frailty increased strikingly after a 5‐days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.