Adverse Events During Supervised Exercise Interventions in Pediatric Oncology—A Nationwide Survey

Objectives: Exercise interventions during and after treatment for pediatric cancer are associated with beneficial physical, psychological, and social effects. However, valid data about adverse events (AEs) of such interventions have rarely been evaluated. This retrospective study evaluates AEs that occurred during supervised oncological exercise programs for pediatric cancer patients and survivors.Methods: This Germany-wide study used a self-administered online survey focusing on general program characteristics and AEs retrospectively for 2019. The questionnaire included (a) basic data on the offered exercise program, (b) AEs with consequences (Grade 2–5) that occurred in 2019 during an exercise intervention, (c) number of Grade 1 AEs, (d) safety procedures as part of the exercise programs, and (e) possibility to give feedback and describe experience with AEs in free text.Results: Out of 26 eligible exercise programs, response rate of program leaders was 92.3% (n = 24). Representatives working for Universities (n = 6), rehabilitation clinics (n = 3), acute cancer clinics (n = 12), and activity camps (n = 3) participated. In total, 35,110 exercise interventions with varying duration were recorded for 2019. Six AEs with consequences (Grade 2–3) occurred during exercise interventions after cancer treatment resulting in an incidence of 17 per 100,000 exercise interventions (0.017%). No life-threatening consequences or death were reported and no serious AE occurred during acute cancer treatment. Grade 1 AE occurred with a frequency of 983, corresponding to an incidence of 2,800 per 100,000 interventions (2.8%). Most frequent Grade 1 AE were muscle soreness, circulatory problems, and abdominal pain. The most frequent preventive safety procedures at the institutions were regular breaks, consultations with the medical treatment team, and material selection with low injury potential.Conclusions: Supervised exercise interventions for pediatric cancer patients and survivors seem to be safe and AEs with consequences comparatively rare when compared to general childhood population data. Occurrence of grade 1 AEs was common, however, causality was probably not evident between AEs and the exercise intervention. Future research should standardize assessment of AEs in clinical practice and research, and prospectively register and evaluate AEs that occur in the context of exercise interventions in pediatric cancer patients and survivors.

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Diet and exercise interventions for pediatric cancer patients during therapy: tipping the scales for better outcomes

Pediatric Research ◽

10.1038/pr.2017.225 ◽

2017 ◽

Vol 83 (1) ◽

pp. 50-56 ◽

Cited By ~ 9

Author(s):

Keri L Schadler ◽

Eugenie S Kleinerman ◽

Joya Chandra

Keyword(s):

Cancer Patients ◽

Pediatric Cancer ◽

Exercise Interventions ◽

Pediatric Cancer Patients ◽

Diet And Exercise

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Mutational Consequences of Chemotherapy in Hematopoietic Stem and Progenitor Cells of Pediatric Cancer Patients

Blood ◽

10.1182/blood-2021-148471 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2154-2154

Author(s):

Eline J.M. Bertrums ◽

Axel Rosendahl-Huber ◽

Jurrian de Kanter ◽

Anais C.N. van Leeuwen ◽

Flavia Peci ◽

...

Keyword(s):

Cancer Treatment ◽

Childhood Cancer ◽

Cancer Patients ◽

Pediatric Cancer ◽

Post Treatment ◽

Chemotherapeutic Drugs ◽

Induced Mutations ◽

Hematopoietic Stem ◽

Pediatric Cancer Patients

Abstract Background Childhood cancer survivors are confronted with a variety of chronic health conditions as a consequence of their life saving therapy. Chemotherapy is the cornerstone of childhood cancer treatment, which consists of combinations of various drugs administered over multiple years. Most chemotherapeutic drugs act by fatally damaging the DNA or blocking the replication thereof. Although high-intensity chemotherapy efficiently eradicates tumor cells, the impact on the genomes of normal, that is noncancerous, cells remains unknown. Mutagenicity of cancer treatment on normal hematopoietic cells may contribute to the development of chronic health conditions later in life, such as therapy-related acute myeloid leukemia (t-AML). Here, we characterized the mutational consequences of chemotherapy in the genomes of hematopoietic stem and progenitor cells (HSPCs) of children treated for cancer. Methods This study was approved by the Biobank and Data Access Committee of the Princess Máxima Center for Pediatric Oncology and all samples were obtained via the in-house biobank. We performed whole-genome sequencing (WGS) on multiple single HSPCs from all patients as well as the t-AML if available. In case of t-AML patients, samples were taken before t-AML treatment. Data on mutation accumulation in HSPCs of healthy individuals from 0-63 years of age was previously acquired. To distinguish the effects of different chemotherapies, we developed an in vitro approach using cord blood HSPCs to experimentally define the mutational consequences of individual chemotherapeutic drugs in primary human cells. Results Our cohort consisted of 22 pediatric cancer patients of which we obtained bone marrow aspirates and/or peripheral blood from timepoints pre- and post-treatment for their first cancer. We included 17 t-AML patients with varying first cancer diagnoses and five acute lymphoblastic leukemia (ALL) patients who did not develop t-AML. Patient characteristics and therapy information is described in Table 1. We compared the mutational burden of pre- and post-treatment HSPCs of the childhood cancer patients to those of healthy treatment-naïve individuals. HSPCs at time of first diagnosis of childhood cancer patients displayed a mutation burden similar to HSPCs of healthy individuals. In contrast, post-treatment HSPCs showed a significantly higher increase in mutation number over time than expected by normal ageing. We used mutational signature analysis to pinpoint the causes of this increased mutation burden in post-treatment HSPCs. Surprisingly, in most of these HSPCs the additive mutational effect could be attributed to clock-like processes, active during normal aging. Only few chemotherapeutic drugs showed direct mutagenic effects, such as platinum drugs and thiopurines. Whereas cisplatin-induced mutations could be observed in all cells exposed to this drug, thiopurine-induced mutations were present in a subset of the exposed HSPCs. These differences in thiopurine-induced mutagenesis across multiple exposed HSPCs could even be observed within individual patients. In one patient, the HSPCs containing the thiopurine-signature shared the oncogenic MLL-rearrangement with the t-AML blasts and had shorter telomeres compared to the HSPCs without this signature. This finding indicates that these cells have undergone more cell divisions, suggesting that thiopurine-induced mutagenesis requires DNA replication. We also identified novel therapy-associated mutational signatures. One of these signatures was observed in multiple patients who received a hematopoietic stem cell transplantation, as part of their cancer treatment, after which they displayed a viral reactivation for which they were treated. By WGS of in vitro exposed cord blood HSPCs, we demonstrated that this signature is caused by the antiviral drug ganciclovir, which is commonly used to treat cytomegalovirus infections. The second signature was present in HSPCs of a patient who received a combination of thiotepa and treosulfan. Conclusions Enhanced mutation accumulation after pediatric cancer treatment is caused by both direct and indirect mechanisms. The variance in mutagenic effects of (chemo)therapies on healthy HSPCs may influence the risk an individual patient has to develop t-AML and could, in future, play a role in t-AML risk assessment of pediatric cancer survivors and the development of new treatment regimens. Figure 1 Figure 1. Disclosures Zwaan: Sanofi: Consultancy.

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Combination therapy with anti-PD-1 or PD-1 antibody alone in pediatric patients with relapsed or refractory cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e22004 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e22004-e22004

Author(s):

Yi Que ◽

Juan Wang ◽

Jia Zhu ◽

Na Li ◽

Junting Huang ◽

...

Keyword(s):

Antitumor Activity ◽

Combination Therapy ◽

Adverse Events ◽

Disease Control ◽

Cancer Patients ◽

Pediatric Cancer ◽

Pediatric Patients ◽

Response Rate ◽

Objective Response ◽

Pediatric Cancer Patients

e22004 Background: There is limited experience of PD-1 combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. Methods: This was an observational retrospective study performed at two academic medical centers (Sun Yat-sen University Cancer Center and Nanfang Hospital, Southern Medical University) The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as well as describing progression free survival (PFS) and overall survival (OS). Results: Of the 22 pediatric cancer patients who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0-43 months). The objective response rate (ORR) and disease control rate (DCR) of the 6 patients with HL were 83.3% (3CR and 2PR) and 100%, respectively. No objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. For patients treated with PD-1 inhibitor combination therapy, PD-1 antibody combined with decitabine showed potential efficacy in advanced pediatric cancer patients. One of the Three of patients who received PD-1 combined with decitabine achieved CR and another two other patients achieved PR. At the data cutoff, 10 of the 13 (76.9%) patients achieved disease control as the best objective response. The median PFS and OS were 90 days (95%CI: 10.733-169.267) and 158 days (95%CI: 131.514-184.486) respectively. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 monotherapy. The severe TRAEs are due to chemotherapy in the combination regimen. Conclusions: PD-1 monotherapy demonstrated antitumor activity in a population of pediatric patients with HL. The regimen of PD-1 inhibitor combined with decitabine showed potential in treating with pediatric cancer patients.

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Effects of Exercise Interventions on Immune Function in Children and Adolescents With Cancer and HSCT Recipients - A Systematic Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.746171 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ronja Beller ◽

Sabrina Bianca Bennstein ◽

Miriam Götte

Keyword(s):

Systematic Review ◽

Immune System ◽

Children And Adolescents ◽

Cancer Patients ◽

Pediatric Cancer ◽

Immune Cell ◽

Systemic Review ◽

Cochrane Library ◽

Exercise Interventions ◽

Pediatric Cancer Patients

BackgroundPediatric cancer patients are at high risk for life-threatening infections, therapy associated complications and cancer-related side effects. Exercise is a promising tool to support the immune system and reduce inflammation. The primary objective of this systematic review was to evaluate the effects of exercise interventions in pediatric cancer patients and survivors on the immune system.MethodsFor this systematic review (PROSPERO ID: CRD42021194282) we searched four databases (MEDLINE, Cochrane Library, ClinicalTrials.gov, SPORTDiscus) in June 2021. Studies with pediatric patients with oncological disease were included as main criterion. Two authors independently performed data extraction, risk of bias assessment, descriptive analysis and a direction ratio was calculated for all immune cell parameters.FindingsOf the 1448 detected articles, eight studies with overall n = 400 children and adolescents with cancer and n = 17 healthy children as controls aged 4-19 years met the inclusion criteria. Three randomized, four non-randomized controlled trials and one case series were analyzed descriptively. The exercise interventions had no negative adverse effects on the immune system. Statistically significant results indicated enhanced cytotoxicity through exercise, while changes in immune cell numbers did not differ significantly. Interventions further reduced days of in-hospitalization and reduced the risk of infections. Several beneficial direction ratios in immune parameters were identified favoring the intervention group.InterpretationExercise interventions for pediatric cancer patients and survivors had no negative but promising beneficial effects on the immune system, especially regarding cytotoxicity, but data is very limited. Further research should be conducted on the immunological effects of different training modalities and intensities, during various treatment phases, and for different pediatric cancer types. The direction ratio parameters given here may provide useful guidance for future clinical trials.Systemic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021194282, Prospero ID: CRD42021194282.

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Development and Evaluation of Video-Based Educational Materials for Nutritional Management of Cancer in Children Among Healthcare Professionals and Caregivers

10.21203/rs.3.rs-870552/v1 ◽

2021 ◽

Author(s):

Nurul Huda Razalli ◽

Hamidah Alias ◽

Mohd Hafizuddin Mohammad ◽

Nur Ruzaireena Rahim ◽

Nur Qharena Alwani Zulkipli

Keyword(s):

Side Effects ◽

Cancer Treatment ◽

Cancer Patients ◽

Pediatric Oncology ◽

Pediatric Cancer ◽

Healthcare Professionals ◽

Nutritional Management ◽

Educational Materials ◽

Nutrition Management ◽

Pediatric Cancer Patients

Abstract Background A good audio-visual educational material for caregivers on nutrition management of pediatric oncology patients can improve treatment effectiveness, recovery rate, and nutritional status of patients. This study aimed to develop and evaluate a series of video-based educational materials for nutritional management of pediatric oncology patients among healthcare professionals and caregivers.Methods The development of the video series began with subtopic selection and content refinement based on a printed booklet project previously published by the groups of five experts in dietetics and oncology medicine and five caregivers of pediatric cancer patients. 10 healthcare professionals (medical doctors and dietitians with over 5 years of working experience) and 15 caregivers then evaluated the video series for acceptability and relevance using the Malay version of the Patient Education Materials Assessment Tools for Audio-Visual materials (PEMAT-AV). Sets of understandability and actionability statements were given a score of 0 (disagree) or 1 (agree), and the overall percentage was calculated.ResultFour main topics were selected from the booklet and adopted into 5 video series ranging from 3 to 8 minutes in length developed in the Malay language entitled (i) Introduction to Cancer and the Treatment, (ii) The Side Effects of Cancer Treatment and Management (Part 1), (iii) The Side Effects of Cancer Treatment and Management (Part 2), (iv) Nutrition Management in Children with Cancer, and (v) You Ask, We Answer. The average understandability and actionability scores rated by the healthcare professionals were 98.6%% and 98.7%respectively. Whereas the caregivers’ average score for understandability was 99.5% and 99.6% for actionability.ConclusionsThe findings revealed that a high-quality video series was successfully developed and rated as highly understandable and actionable by both healthcare professionals and caregivers. This reflects positive acceptance and relevance of the nutritional management educational videos by both groups who manage and care for pediatric cancer patients. Trial RegistrationCentre for Research and Instrumentation Management, Research Ethics Committee of The National University of Malaysia; Ref. No. UKM/PPI/111/8/JEP-2021-266

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Impact of severe oral mucositis in pediatric cancer patients on resource utilization and cancer treatment plans

International Journal of Clinical Pharmacy ◽

10.1007/s11096-021-01253-y ◽

2021 ◽

Cited By ~ 2

Author(s):

Farah Alsheyyab ◽

Deema Al-Momani ◽

Rawan Kasht ◽

Aya Kamal ◽

Dana Abusalem ◽

...

Keyword(s):

Cancer Treatment ◽

Cancer Patients ◽

Resource Utilization ◽

Oral Mucositis ◽

Pediatric Cancer ◽

Pediatric Cancer Patients ◽

Treatment Plans ◽

Severe Oral Mucositis

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A Systematic Review of the Safety, Feasibility and Benefits of Exercise for Patients with Advanced Cancer

Cancers ◽

10.3390/cancers13174478 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4478

Author(s):

Nico De Lazzari ◽

Timo Niels ◽

Mitra Tewes ◽

Miriam Götte

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Cancer Patients ◽

Advanced Cancer ◽

Exercise Intervention ◽

Cochrane Library ◽

Controlled Trials ◽

Advanced Cancer Patients ◽

Exercise Interventions ◽

Positive Effects

Exercise therapy is a common supportive strategy in curative cancer treatment with strong evidence regarding its positive effects on, for example, cancer-related fatigue, health- related quality of life, and physical function. In the field of advanced cancer patients, knowledge about exercise as a useful supportive strategy is missing. The aim of this systematic review was to evaluate the feasibility and safety of exercise interventions as well as its effects on lowering the symptom burden. We included randomized controlled trials and nonrandomized controlled trials with advanced cancer patients receiving any type of exercise intervention. After an extensive literature search (in accordance to PRIMSA guidelines) in PubMed, Cochrane Library, and SPORTDiscus, 14 studies including 940 participants with different cancer entities were eligible. The results indicated the safety of exercise. In total, 493 participants received exercise interventions, with nine adverse events and no severe adverse events. The median recruitment rate was 68.33%, and adherence to exercise intervention was 86%. Further research with a high-quality and larger sample size is needed to clarify the potential of exercise with advanced cancer patients. Different advanced cancer entities have distinguished symptoms, and future research should construct entities-specific trial populations to figure out the best supportive exercise interventions.

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