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Children with cancer commonly experience distressing symptoms such as pain, fatigue and nausea. Improvements in patient outcomes have been associated with implementation of clinical practice guideline-consistent care across several domains. The objective of this study was to develop a process to identify symptom management clinical practice guidelines (CPGs) applicable to children and adolescents receiving cancer treatments. We focused on identifying CPGs to manage 15 symptoms. The process defined three Tiers of CPGs based upon applicability to pediatric cancer patients and ease of identification: Tier 1: endorsed by the Children’s Oncology Group; Tier 2: housed in the Emergency Care Research Institute repository, or developed by the American Society of Clinical Oncology or National Institute for Health and Care Excellence; and Tier 3: identified by systematic review. We first searched for CPGs published 2015–2020 and identified Tiers 1 or 2 CPGs. If unavailable or scope was too narrow, we proceeded to Tier 3. If CPGs were not identified, we repeated these steps for CPGs published 2010–2014. There were six Tier 1 and 13 Tier 2 CPGs published 2015–2020 across the 15 symptoms. Four symptoms required progression to Tier 3 because CPGs were absent (anger) or because scope was too narrow (pain, anorexia/excessive hunger and diarrhea). The systematic review identified three CPGs for pain and none for the other three symptoms. In total, CPGs were identified for 14 of 15 symptoms. None were identified for anger. We created a process to identify supportive care CPGs for pediatric cancer symptom management and were able to identify CPGs that addressed 14 of 15 symptoms. Future work should focus on evaluating implementation techniques for these CPGs and determining the impact of these CPGs on provider and patient outcomes.

Introduction: We aimed to create a Spanish-language version of the Pediatric Nausea Assessment Tool (PeNAT) and examine its understandability among Spanish-speaking, Hispanic American children. Methods: Translation: Forward and backward translations of the PeNAT documents were performed and verified by a bilingual panel. Four monolingual, Spanish-speaking dyads (child/parent) and four bilingual dyads piloted the Spanish-language PeNAT documents. Four additional bilingual dyads read both versions and completed the PeNAT using their preferred version. These were reviewed for errors due to misunderstanding. Understandability: Children aged 4–18 years about to receive chemotherapy who spoke Spanish at home and were without impairments precluding PeNAT use were eligible. Participants used the Spanish-language PeNAT during a chemotherapy block. Parents gave feedback on the PeNAT documents. Recruitment continued until 10 consecutive participants offered no substantive suggestions for revision. Results: Translation: All child/parent dyads completed the PeNAT without errors attributable to misunderstanding. The Spanish-language PeNAT was preferred by three of four bilingual dyads. Understandability: Ten cancer patients (mean age: 10.6 years) used the Spanish-language PeNAT. All parents felt their child understood the PeNAT; none felt the documents were hard or very hard to use. Conclusion: The Spanish-language PeNAT was understood by Spanish-speaking Hispanic American children. Further psychometric testing is warranted.

Chemotherapy-induced nausea and vomiting (CINV) continue to negatively influence the quality of life of both adult and pediatric cancer patients (Dupuis et al., 2010; Farrell et al., 2013; Russo et al., 2014; Hinds et al., 2009; Sommariva et al., 2016). Vomiting and retching are symptoms that can be assessed objectively while nausea, a subjective symptom, is more difficult to quantify. Adult cancer patients can usually describe the severity of the nausea they feel using self-report visual analog or adjectival rating scales. Instruments such as the Multinational Association of Supportive Care in Cancer Antiemesis Tool (available from www.mascc.org) have been validated for this purpose and are recommended by experts in the field (Hesketh et al., 2015).

PURPOSE To develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. METHODS Recommendations were developed by an international multidisciplinary panel that included a patient advocate. We conducted a systematic review of systemic antifungal prophylaxis in children and adults with cancer and HSCT recipients. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to make strong or weak recommendations and to classify level of evidence as high, moderate, low, or very low. The panel considered directness of the data to pediatric patients. RESULTS There were 68 randomized trials included in the systematic review, of which 6 (9%) were conducted in a solely pediatric population. Strong recommendations were made to administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia, to those undergoing allogeneic HSCT pre-engraftment, and to those receiving systemic immunosuppression for graft-versus-host disease treatment. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. For children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested. Posaconazole may also be used in those age 13 years or older. A strong recommendation against routine administration of amphotericin as systemic antifungal prophylaxis was made. CONCLUSION We developed a clinical practice guideline for systemic antifungal prophylaxis administration in pediatric patients with cancer and HSCT recipients. Implementation and assessment of guideline-concordant rates and impacts are important future steps.

PURPOSE To update the guideline to include new anticancer agents, antiemetics, and antiemetic regimens and to provide recommendations on the use of dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors (CPIs). METHODS ASCO convened an Expert Panel and updated the systematic review to include randomized controlled trials (RCTs) and meta-analyses of RCTs published between June 1, 2016, and January 24, 2020. To address the dexamethasone and CPI question, we conducted a systematic review of RCTs that evaluated the addition of a CPI to chemotherapy. RESULTS The systematic reviews included 3 publications from the updated search and 10 publications on CPIs. Two phase III trials in adult patients with non–small-cell lung cancers evaluating a platinum-based doublet with or without the programmed death 1 (PD-1) inhibitor pembrolizumab recommended that all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. In both studies, superior outcomes were noted in the PD-1 inhibitor–containing arms. Other important findings address olanzapine in adults and fosaprepitant in pediatric patients. RECOMMENDATIONS Recommendations for adults are unchanged with the exception of the option of adding olanzapine in the setting of hematopoietic stem cell transplantation. Dosing information now includes the option of a 5-mg dose of olanzapine in adults and intravenous formulations of aprepitant and netupitant-palonosetron. The option of fosaprepitant is added to pediatric recommendations. There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy. CPIs administered alone or in combination with another CPI do not require the routine use of a prophylactic antiemetic. Additional information is available at www.asco.org/supportive-care-guidelines .

PURPOSE To identify factors associated with chemotherapy-induced vomiting (CIV) control in pediatric patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS An individual, patient‐level, pooled analysis was performed using data from five clinical trials of aprepitant or fosaprepitant in pediatric patients receiving HEC or MEC. The proportion of individuals who experienced no vomiting (complete CIV control) during the phase of interest was the primary study end point. The association of acute-phase complete CIV control (from first chemotherapy dose to 24 hours after the last chemotherapy dose of the chemotherapy block) with age, sex, race, cancer type, acute-phase duration, and antiemetic regimen was examined. Association of the same factors and acute-phase complete CIV control with complete CIV control in the delayed phase (end of acute phase until ≤ 96 hours later) was examined. RESULTS A total of 735 patients (mean age, 8.9 years; range, 0.3 to 17.9 years) were included in the acute-phase analysis. Acute-phase complete CIV control was less likely in older patients (relative risk [RR], 0.97 per year; 95% CI, 0.96 to 0.98 per year) and longer acute-phase duration (RR, 0.89 per day; 95% CI, 0.84 to 0.94 per day). Receipt of ondansetron plus aprepitant or fosaprepitant was associated with a higher likelihood of acute-phase complete CIV control versus ondansetron alone (RR, 1.28; 95% CI, 1.09 to 1.50). Delayed-phase complete CIV control was more likely in patients with acute-phase complete CIV control (RR, 1.19; 95% CI, 1.06 to 1.34) and in those who received aprepitant or fosaprepitant. CONCLUSION Younger age, shorter acute-phase duration, and antiemetic regimen were associated with acute-phase complete CIV control in pediatric patients receiving HEC or MEC. Acute-phase complete CIV control and antiemetic regimen were associated with delayed-phase complete CIV control.

Change in hunger is a common and bothersome symptom among pediatric patients receiving cancer treatments. Objectives were to describe how children and adolescents receiving cancer treatments experience changes in hunger, factors associated with both increases and decreases in hunger, and coping strategies used by these patients. We enrolled children and adolescents 4–18 years of age with cancer or hematopoietic stem cell transplantation (HSCT) recipients who were actively receiving treatment or who had completed therapy. Using a single, qualitative, semi-structured interview, we asked participants about the experience of increases or decreases in hunger, including characteristics of the change and identified coping strategies. There were 50 children enrolled; 25 (50%) were 4–10 years of age and 33 (66%) were boys. Most often, patients associated an increase in hunger with corticosteroid administration, while other treatments, accompanying symptoms, inactivity, and the hospital environment were associated with a decrease in hunger. Many reported that no coping strategies were successful. For those who did report successful strategies to manage an increase in hunger, these included sleep and having food available. Strategies used to manage a decrease in hunger included anti-emetic medications, increased caloric intake, varied food choices, encouragement to eat, scheduling or tracking of meals, and physical activity. Both increases and decreases in hunger were commonly described. Some coping strategies were reported to be successful. Further research should identify and test interventions to manage changes in hunger in pediatric cancer patients.

PURPOSE: Prescribing guideline-recommended anti-emetics is an effective strategy to prevent CINV. However, the rate of guideline-concordant care is not well-understood. The purpose of this study was to describe the proportion of pediatric, adolescent, and young adult patients receiving HEC or MEC who received guideline-concordant antiemetic prophylaxis for acute CINV, and to identify potential predictors of guideline-concordant antiemetic prophylaxis. METHODS: Using electronic health record data from 2016 through 2018, a retrospective single-institution cohort study was conducted to investigate how often patients less than 26 years of age receiving moderately or highly emetogenic chemotherapy receive guideline-concordant prophylaxis for acute CINV. Guideline-concordant care was defined according to guidelines from the Pediatric Oncology Group of Ontario for patients < 18 years and the American Society of Clinical Oncology for those ≥ 18 years. Independent variables included: sex, age, insurance status, race, ethnicity, cancer type, chemotherapy regimen, clinical setting, chemotherapy emetogenicity, and patient location. Predictors of receiving guideline-concordant care were determined using multiple logistic regression. RESULTS: Of 180 eligible patients, 65 (36.1%) received guideline-concordant care. In multivariable analysis, being treated in adult oncology setting (aOR: 14.3, CI(95): 5.3 – 38.6), with a cisplatin-based regimen (aOR: 3.5, CI(95):1.4 – 9.0), solid tumor diagnosis (aOR: 2.2, CI(95): 1.0 – 4.8), and commercial insurance (aOR: 2.4, CI(95): 1.1 – 5.2) were associated with significantly higher likelihood of receiving guideline-concordant care. CONCLUSIONS: Multi-level factors were associated with receiving guideline concordant care for prevention of CINV in children, adolescents, and young adults receiving emetogenic chemotherapy. These findings can inform current efforts to optimize implementation strategies for supportive care guidelines

Background Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT. Methods An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. Results The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. Conclusions We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis., This clinical practice guideline presents recommendations for systemic antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation patients. The recommendations were developed by an international panel based on the results of a systematic review of 114 randomized trials.

Background Objectives were to describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation. Methods We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators prior to randomization to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of the COVID-19 pandemic on clinical research. The Wilcoxon rank sum test was used to compare characteristics of institutions that agreed that their department supported the implementation of symptom management care pathways vs. institutions that did not agree. Results Of the 25 sites, one withdrew because of resource constraints and one did not respond, leaving 23 institutions. Among the seven CFIR constructs, the least supported was implementation climate; 57% agreed there was support, 39% agreed there was recognition and 39% agreed there was prioritization for symptom management care pathway implementation at their institution. Most common barriers were lack of person-time to create care pathways and champion their use (35%), lack of interest from physicians (30%) and lack of information technology resources (26%). Most sites reported no negative impact of the COVID-19 pandemic across research activities. Sites with fewer pediatric cancer patients were more likely to agree that staff are supported to implement symptom management care pathways (P = 0.003). Conclusions The most commonly reported barriers to implementation were lack of support, recognition and prioritization. The COVID-19 pandemic may not be a major barrier to clinical research activities in pediatric oncology.

OBJECTIVE: To describe the experiences and perspectives of parents of pediatric patients with acute lymphoblastic leukemia (ALL) regarding oral chemotherapy administration during maintenance therapy. METHODS: English-speaking parents of patients 4 to

ObjectivesSymptom Screening in Pediatrics Tool (SSPedi) is a validated self-report symptom screening tool for patients with cancer 8–18 years of age. Co-SSPedi is a novel dyad approach in which both child and parent complete SSPedi together. The objective was to finalise the approach to co-SSPedi administration with instruction that is easy to understand, resulting in dyads completing co-SSPedi correctly.MethodWe enrolled child and parent dyads, who understood English and where children (4–18 years) had cancer or were hematopoietic stem cell transplantation recipients. We provided each dyad with instruction on how to complete co-SSPedi together. Mixed methods were used to determine how easy or hard the instruction was to understand. Two raters adjudicated if co-SSPedi was completed correctly. Dyads were enrolled in cohorts of 12 evenly divided by age (4–7, 8–10, 11–14 and 15–18 years).ResultsWe enrolled 5 cohorts of 12 dyads, resulting in 60 dyads. Following verbal instruction provided in the first cohort, we identified the need for written instruction emphasising children should wait for parent response prior to entering scores. The instruction was iteratively refined based on qualitative feedback until the fifth cohort, where all 12 dyads found the instruction easy to understand and completed co-SSPedi correctly.ConclusionsWe developed a standard approach to dyad symptom screening named co-SSPedi with instruction that is easy to understand, resulting in correct co-SSPedi completion. Future efforts should focus on co-SSPedi validation and understanding how co-SSPedi scores compare to self- or proxy-reported symptom reporting.

Background: Features of clinical practice guideline (CPG) recommendations may affect understanding and consequently successful uptake and implementation. We aimed to develop a recommendation format to improve understandability among healthcare professionals involved in pediatric cancer care.Methods: We conducted a multi-center qualitative study of health care professionals at participating pediatric oncology sites. We developed an initial format based on the current literature and used the “think-aloud” technique in multiple rounds of one-on-one cognitive interviews to iteratively improve it. Interviews were conducted until the format was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to the understandability of the recommendation. Results: Five investigators interviewed 33 healthcare professionals from multiple disciplines in seven rounds. We identified important factors influencing how to communicate recommendations. Regarding the strength of the recommendation, participants found understanding weak recommendations more challenging than strong. Understanding was improved by using the word ‘conditional’ instead of ‘weak’. Participants believed the inclusion of a rationale section to be very helpful. More information was desirable when a recommendation entailed a practice change. Although participants wanted additional information, they were concerned that there could be too much information. They, therefore, suggested that key words and the studies included in the evidence synthesis be hyperlinked to explanatory data. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the rationale section describes the benefits and harms and additional factors, such as implementation, that were balanced by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable. Conclusions: A well-understood recommendation format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users.

There is growing recognition of the degree to which symptoms negatively impact on children receiving cancer treatments. A recent study described that almost all inpatient pediatric oncology patients are experiencing at least one bothersome symptom and almost 60% are experiencing at least one severely bothersome symptom. Poor symptom control occurs because of challenges with communication of bothersome symptoms to clinicians, lack of clinical practice guidelines (CPGs) for most of these symptoms, and failure to administer preventative and therapeutic interventions known to be effective for symptom control. This article reviews approaches used to improve symptom control for children receiving cancer treatments. Areas addressed include systematic symptom screening and creation of CPGs for symptom management. Challenges with electronic health integration are also addressed. Several multi-symptom assessment scales have been developed but none have yet been used to directly influence patient management. The number of CPGs applicable to symptom control in pediatric oncology is increasing but remains small. Improving the creation of and adherence to CPGs for symptom management is an important priority. Finally, identifying ways that symptom management systems can be integrated into clinical work flows is essential; these will likely need to focus on electronic health records.

PURPOSE To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT). METHODS We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia. RESULTS Of 20 984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified. CONCLUSIONS Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required.

Changes in taste is a common bothersome symptom in children receiving cancer treatments. However, little is known about how pediatric cancer patients experience this symptom. The objective was to describe how children receiving cancer treatments experience taste alterations and the approaches they use to address the issue. In this qualitative study, we included English-speaking children 4–18 years of age with cancer or hematopoietic stem cell transplantation recipients who were actively receiving cancer treatment or who had completed therapy. Using a semi-structured questionnaire, we asked questions about the experience of altered taste sensation. We asked about its characteristics, impacts and identified coping strategies. We included 50 children. Children experienced changes in taste in a heterogeneous fashion although commonly described food as tasting “different”, “not right” or “funny”. While change in food preferences due to taste alterations was common, specific choices varied. Many found changes started with treatment initiation or mid-way through treatment, and some found that symptoms persisted up to 9 months following treatment completion. Actions taken to address taste changes were sucking on candy, brushing teeth and modifying food choices. The experience of changes in taste was common yet highly variable in its presentation and resultant changes in food preferences. Taste changes did not always resolve soon after treatment completion. Future research should identify ways to manage this symptom in pediatric cancer patients.

Little evidence exists regarding the emetogenicity of chemotherapy in pediatric patients. This study describes the prevalence of chemotherapy-induced nausea and vomiting (CINV) in pediatric patients receiving etoposide plus ifosfamide over 5 days, a common pediatric regimen. English-speaking, non-chemotherapy-naive patients aged 4 to 18 years about to receive etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day over 5 days participated. Antiemetic prophylaxis was determined by each patient’s care team. Emetic episodes were recorded and nausea severity was assessed by patients beginning with the first chemotherapy dose, continuing until 24 h after the last chemotherapy dose (acute phase) and ending 7 days later (delayed phase). The proportion of patients experiencing complete acute CINV control (no nausea, no vomiting, and no retching), the primary study endpoint, was described. The prevalence of complete chemotherapy-induced vomiting (CIV) and chemotherapy-induced nausea (CIN) during the acute, delayed, and overall (acute plus delayed) phases; complete delayed and overall CINV control; and anticipatory CINV were also determined. Twenty-four patients participated; acute CINV was evaluable in 22. Most (75%; 18/24) received a 5-HT3 antagonist plus dexamethasone for antiemetic prophylaxis. Few (23%; 5/22) experienced complete acute CINV control. Complete acute CIV and CIN control were experienced by 57% (13/23) and 27% (6/22) of patients, respectively. Complete delayed CINV, CIV, and CIN control rates were 42% (8/19), 70% (14/20), and 42% (8/19), respectively. Our findings support the classification of etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day IV over 5 days as highly emetogenic. This information will optimize antiemetic prophylaxis selection and CINV control in pediatric patients.

Background Objectives were to describe the proportion of bothersome symptoms self-reported using the Symptom Screening in Pediatrics Tool (SSPedi) documented in the medical records and associated with an intervention. Methods Eligible respondents were inpatients aged 8–18 years receiving cancer treatments and expected to be in hospital or clinic three days later. Children self-reported symptom bother using SSPedi. We evaluated symptom documentation and interventions in the medical records proximal to SSPedi administration. Results There were 168 children included. Symptoms rated as at least ‘a lot’ bother were documented in the medical record less than 60% of the time for 12 of 15 symptoms. Of these symptoms, the most infrequently documented symptoms were problems with thinking or remembering things (0%), changes in how your body or face look (4.8%), changes in taste (7.7%) and tingly or numb hands or feet (11.1%). Intervention provision for symptoms rated as ‘a lot’ bother occurred less than 60% of the time for 10 of 15 symptoms. Of these symptoms, the most infrequently treated were thinking or remembering things (0%), changes in how your body or face look (0%), tingly or numb hands or feet (0%), changes in taste (0%), diarrhoea (0%) and feeling tired (1.6%). Conclusions Documentation of symptoms and intervention provision were generally infrequent. Symptoms that were almost never documented or treated included problems with cognition, body image, taste changes and peripheral neuropathy. Future efforts should incorporate symptom screening into routine care and facilitate symptom management by improving access to evidence-based clinical practice guidelines.

Chemotherapy-induced nausea and vomiting (CINV) are among the most distressing and feared treatment-related adverse effects for cancer patients. Selection of antiemetic agents to prevent CINV should be based on an evaluation of their efficacy and safety. This systematic review and meta-analysis describes the adverse effects associated with antiemetic agents recommended for the prevention of acute CINV in children by clinical practice guidelines (CPGs). Areas covered: A systematic literature search was conducted using four databases to identify papers describing adverse effects in pediatric patients receiving aprepitant, dexamethasone, granisetron, ondansetron, palonosetron, or tropisetron. Meta-analysis was conducted for adverse effects reported in at least three prospective studies with a cumulative incidence of at least 1%. Expert opinion: Antiemetic agents currently recommended by CPGs are relatively safe to use in children. The presence of patient-specific risk factors for rare adverse effects, especially cardiac arrhythmia, should be evaluated when selecting a patient's antiemetic therapy. Evaluation of the long-term safety of CPG-recommended antiemetic agents in pediatric cancer patients is needed.

Background The Symptom Screening in Pediatrics Tool (SSPedi) is valid for assessing symptoms in children aged 8–18 years receiving cancer treatments. The objective was to develop a new self-report symptom screening tool for children receiving cancer treatments who are 4–7 years of age (mini-SSPedi), based on SSPedi. Methods Respondents were children with cancer or pediatric hematopoietic stem cell transplantation (HSCT) recipients who were 4–7 years of age. We included the same 15 symptoms contained in SSPedi. Using cognitive interviewing, we developed mini-SSPedi in three phases and made decisions based upon respondent understanding. First, we developed questionnaire structure regarding recall period, concept of bother and response option format. Second, we determined wording of each symptom. Third, we evaluated the entire mini-SSPedi instrument for understanding and ease of completion. Results We enrolled 100 participants in total and included 30, 40 and 30 in each of the three phases. Questionnaire structure was satisfactory with a recall period of “today” and a faces-based 3-point Likert scale. Bother was well-understood. Five symptoms required modification to achieve satisfactory understanding while the remaining 10 SSPedi symptoms did not require modification. Among the last 10 children enrolled, all understood each mini-SSPedi item and none thought mini-SSPedi was hard to complete. Conclusion We developed a symptom screening tool for children with cancer and pediatric HSCT recipients between 4 and 7 years of age that is understandable and easy to complete. Future work will evaluate the psychometric properties of mini-SSPedi and develop an electronic version of the instrument. Electronic supplementary material The online version of this article (10.1186/s12885-018-5210-z) contains supplementary material, which is available to authorized users.

Objectives were to describe bothersome fatigue in children with cancer and hematopoietic stem cell (HSCT) recipients and to identify factors associated with severely bothersome fatigue. We included children ages 8–18 years treated for cancer or HSCT recipients from three groups: [1] receiving active cancer treatment and admitted to hospital for at least 3 days, [2] attending outpatient clinic for acute lymphoblastic leukemia maintenance therapy, and [3] attending outpatient clinic following treatment completion. Fatigue was measured using the Symptom Screening in Pediatrics Tool (SSPedi); severely bothersome fatigue was defined as a lot or extremely bothersome fatigue (score of 3–4 on 0–4 scale). Factors associated with severely bothersome fatigue were examined using univariate and multiple logistic regression. Of 502 children included, 414 (82.5%) reported some degree of bothersome fatigue (scores 1–4), and 123 (24.5%) reported severely bothersome fatigue (score 3 or 4). In multiple regression analysis, factors significantly associated with severely bothersome fatigue were child age 11–14 and 15–18 years vs 8–10 years (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.21–3.77 and OR 2.96, 95% CI 1.66–5.44), and inpatients receiving cancer treatment vs outpatients who had completed therapy (OR 3.85, 95% CI 2.17–7.27). We found that 82.5% of children with cancer or HSCT recipients reported bothersome fatigue and 24.5% of children reported severely bothersome fatigue. Risk factors for severely bothersome fatigue were older age and inpatients receiving active cancer treatment. Future work should evaluate systematic symptom screening in clinical practice and apply interventions to reduce fatigue.

Objectives were to describe bothersome self-reported changes in taste in pediatric oncology and hematopoietic stem cell (HSCT) patients and to identify patient and treatment-related factors associated with bothersome taste changes. We prospectively enrolled children and adolescents with cancer or pediatric HSCT recipients 8–18 years of age from three groups: inpatients receiving cancer treatments; outpatients in maintenance therapy for acute lymphoblastic leukemia (ALL); and outpatients in survivorship. Bothersome changes in taste was self-reported using the Symptom Screening in Pediatrics Tool (SSPedi); nausea was self-reported using the Pediatric Nausea Assessment Tool (PeNAT). Among the 502 children included, 226 (45.0%) reported bothersome taste changes and 48 (9.6%) reported severely bothersome taste changes. In multiple regression, factors independently associated with severely bothersome taste changes were: inpatients receiving cancer treatments vs outpatients in survivorship (odds ratio (OR) 12.28, 95% confidence interval (CI) 2.50–222.27), ALL in maintenance vs outpatients in survivorship (OR 7.43, 95% CI 1.06–147.77), current nausea (OR 1.59, 95% CI 1.04–2.42), vomiting (OR 2.18, 95% CI 1.06–4.38), and first language not English (OR 2.09, 95% CI 0.97–4.28). We found that 45% of children with cancer and pediatric HSCT recipients reported bothersome changes in taste and these were severely bothersome in 9.6% of children. Inpatients receiving cancer treatment, those experiencing more nausea and vomiting and children whose first language was not English were at greater risk of severely bothersome changes in taste. Future work should evaluate systematic symptom screening in clinical practice and identify interventions focused on addressing bothersome taste changes.

This 2021 clinical practice guideline update provides recommendations for preventing anticipatory chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. Recommendations are based on systematic reviews that identified (1) if a history of acute or delayed CINV is a risk factor for anticipatory CINV, and (2) interventions for anticipatory CINV prevention and treatment. A strong recommendation to optimize acute and delayed CINV control in order to prevent anticipatory CINV is made. Conditional recommendations are made for hypnosis, systematic desensitization, relaxation techniques, and lorazepam for the secondary prevention of anticipatory CINV. No recommendation for the treatment of anticipatory CINV can be made.

Purpose To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients. Methods We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis. Results We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31–0.76; palifermin RR 0.81 and 95% CI 0.69–0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27–0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects. Conclusions Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620–750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.

Background Clinical practice guideline (CPG)-consistent care improves patient outcomes, but CPG implementation is poor. Little is known about CPG implementation in pediatric oncology. This study aimed to understand supportive care CPG implementation facilitators and barriers at pediatric oncology National Cancer Institute (NCI) Community Oncology Research Program (NCORP) institutions. Methods Healthcare professionals at 26 pediatric, Children's Oncology Group-member, NCORP institutions were invited to participate in face-to-face focus groups. Serial focus groups were held until saturation of ideas was reached. Supportive care CPG implementation facilitators and barriers were solicited using nominal group technique (NGT), and implementation of specific supportive care CPG recommendations was discussed. Notes from each focus group were analyzed using a directed content analysis. The top five themes arising from an analysis of NGT items were identified, first from each focus group and then across all focus groups. Results Saturation of ideas was reached after seven focus groups involving 35 participants from 18 institutions. The top five facilitators of CPG implementation identified across all focus groups were organizational factors including charging teams with CPG implementation, individual factors including willingness to standardize care, user needs and values including mentorship, system factors including implementation structure, and implementation strategies including a basis in science. The top five barriers of CPG implementation identified were organizational factors including tolerance for inconsistencies, individual factors including lack of trust, system factors including administrative hurdles, user needs and values including lack of inclusivity, and professional including knowledge gaps. Conclusions Healthcare professionals at pediatric NCORP institutions believe that organizational factors are the most important determinants of supportive care CPG implementation. They believe that CPG-consistent supportive care is most likely to be delivered in organizations that prioritize evidence-based care, provide structure and resources to implement CPGs, and eliminate implementation barriers. Trial registration ClinicalTrials.gov Identifier: NCT02847130. Date of registration: July 28, 2016.

Background: To describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation. Methods: We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of the COVID-19 pandemic on clinical research. The Wilcoxon rank sum test was used to compare characteristics of institutions that agreed that their department supported the implementation of symptom management care pathways vs. institutions that did not agree.Results: Of the 25 sites, one withdrew because of resource constraints and one did not respond, leaving 23 institutions. Among the seven CFIR constructs, the least supported was implementation climate; 57% agreed there was support, 39% agreed there was recognition and 39% agreed there was prioritization for symptom management care pathway implementation at their institution. Most common barriers were lack of person-time to create care pathways and champion their use (35%), lack of interest from physicians (30%) and lack of information technology resources (26%). Most sites reported no negative impact of the COVID-19 pandemic across research activities. Sites with fewer pediatric cancer patients were more likely to agree that staff are supported to implement symptom management care pathways (P=0.003). Conclusions: The most commonly reported barriers to implementation were lack of support, recognition and prioritization. The COVID-19 pandemic was not a major barrier to clinical research activities in pediatric oncology.Clinical Trial Registration: NCT04614662

ObjectiveChildhood and adolescent cancer can result in high burden of distressing symptoms, particularly in high-risk malignancies. The Symptom Screening in Pediatrics Tool (SSPedi) is a reliable and valid approach to measure bothersome symptoms in paediatric patients receiving cancer treatments. Objective was to describe the feasibility of using SSPedi administration among paediatric patients with high-risk malignancies.MethodsWe conducted a single-centre, cross-sectional study of patients aged 8–18 years with high-risk malignancies in a French paediatric oncology unit. Patients self-reported the degree of bothersome symptoms using SSPedi and difficulty with SSPedi completion. The total SSPedi Score ranging from 0 to 60 (where 60 is worst) and most common moderately bothersome symptoms (scored ≥2 on 0–4 Likert Scale) were described. Feasibility was defined as more than 75% of patients agreeing to participate and more than 90% completion of SSPedi questionnaire.ResultsOut of 16 patients approached, 1 declined participation. Median age was 13 years (IQR 8–19). All were able to self-report SSPedi without difficulty. Patients experienced a median number of 6 (range 0–15) bothersome symptoms (score >0). The mean total SSPedi Score was 12 (SD=9.4). Most common moderately bothersome symptoms were pain (8/15), changes in hunger (8/15) and feeling tired (7/15).ConclusionPatient-reported symptom assessment among children and adolescents with high-risk malignancies is feasible using SSPedi. These patients experience a high burden of bothersome symptoms.

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy-induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose-finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT3 antagonist and five in conjunction with a 5HT3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta-analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research.

Our purpose was to compare conventional meta-analysis and network meta-analysis to evaluate the efficacy of different prophylactic systemic antibiotic classes in patients undergoing chemotherapy or haematopoietic stem cell transplant (HSCT). We included randomised trials if patients had cancer or were HSCT recipients and the intervention was systemic antibacterial prophylaxis. Three types of control groups were used: (1) placebo, no antibiotic and non-absorbable antibiotic separately; (2) placebo and no antibiotic combined; and (3) all three combined. These gave different network geometries. Strategies synthesised were fluoroquinolone, trimethoprim-sulfamethoxazole, cephalosporin and parenteral glycopeptide versus control groups. In total 113 trials met the eligibility criteria. Where treatment effects could be estimated with both conventional and network meta-analysis, values were generally similar. However, where events were sparse, network meta-analysis could be more precise. For example, trimethoprim-sulfamethoxazole versus placebo for infection-related mortality showed a relative risk ratio (RR) of 0.55, 95% CI (0.21 to 1.44) with conventional, and RR 0.43, 95% credible region (0.20 to 0.82) with network meta-analysis. Cephalosporin versus fluoroquinolone was comparable only indirectly using the network approach and yielded RR 0.59, 95% credible region (0.28 to 1.20) to reduce bacteraemia. Incoherence (difference between direct and indirect estimates raising concerns about network meta-analysis validity) was observed with network geometry where control groups were separated, but not where control groups were combined. In this situation, conventional and network meta-analysis yielded similar results in general. Network meta-analysis results could be more precise when events were rare. Some analysis could only be performed with the network approach. These results identify scenarios in which network meta-analysis may be advantageous.

Survival for high-risk neuroblastoma patients is still suboptimal. Although stem cell transplantation (SCT) is used, there is no consensus as to which conditioning regimen has the greatest efficacy and fewest toxicities. We assessed the incidence of and risk for hepatic veno-occlusive disease (VOD) for neuroblastoma patients who underwent autologous SCT with busulfan and melphalan (BuMel) at eight centers following Children's Oncology Group (COG)-based induction chemotherapy. Data regarding the patients, SCT characteristics, busulfan steady-state concentrations, incidence of VOD, and survival were evaluated. VOD was defined using the modified Seattle criteria. Possible factors associated with VOD (age, busulfan-pharmacokinetic parameters, history of hepatic dysfunction, and day of neutrophil engraftment) were evaluated. Seventy five patients were included and 23 children (31%) developed VOD at a median of 19 days after SCT (range 14-27 days). VOD was the cause of death in 4 patients (5%). In a multivariable analysis, young age (OR 1.7 (95% CI: 1.16-2.56; p = 0.012)) and early day of neutrophil engraftment (OR 1.4 (95% CI: 1.08-2.14; p = 0.041) were associated with the development of VOD. Initial or cumulative busulfan steady-state concentration were not associated with VOD. We found that despite the use of intravenous busulfan with adjusted serum levels, the incidence of VOD remains high in pediatric neuroblastoma patients.

Background: Children with cancer often undergo long treatment trajectories involving repeated needle procedures that potentially cause pain and distress. As part of a comprehensive effort to develop clinical practice guidelines (CPGs) to address pain prevention and management in children with cancer, we aimed to provide recommendations on the pharmacological and psychological management of procedure-related pain and distress. Methods: Of the international inter-disciplinary CPG development panel (44 individuals), two working groups including 13 healthcare professionals focused on procedural pain and distress. Grading of Recommendations Assessment, Development and Evaluation methodology was used, including the use of systematic literature reviews to inform recommendations and the use of evidence to decision frameworks. At an in-person meeting in February 2018, the guideline panel discussed these frameworks and formulated recommendations which were then discussed with a patient-parent panel consisting of 4 survivors and 5 parents. Results: The systematic reviews led to the inclusion of 48 randomised controlled trials (total number of participants = 2271). Quality of evidence supporting the recommendations ranged from very low to moderate. Strong recommendations were made for the use of topical anesthetics in all needle procedures, for offering deep sedation (DS)/general anesthesia (GA) to all children undergoing lumbar puncture, for the use of DS/GA in major procedures in children of all ages, for the use of hypnosis in all needle procedures and for the use of active distraction in all needle procedures. Conclusion: In this CPG, an evidence-based approach to manage procedure-related pain and distress in children with cancer is presented. As children with cancer often undergo repeated needle procedures during treatment, prevention and alleviation of procedure-related pain and distress is of the utmost importance to increase quality of life in these children and their families. (C) 2020 The Authors. Published by Elsevier Ltd.

Background Many children undergoing hematopoietic stem cell transplantation (HSCT) experience chemotherapy-induced nausea and vomiting (CINV) despite receiving prophylaxis. Guideline-consistent CINV prophylaxis includes dexamethasone, but uncertainty with regard to safety potentially limits the use of dexamethasone in children. We describe immediate adverse events (AEs) attributable to dexamethasone given for CINV prophylaxis to children during HSCT conditioning. Materials and methods Children enrolled in a previous prospective study were retrospectively analyzed. Objective parameters related to specific AEs occurring within 5 days of dexamethasone administration were abstracted from health records and graded according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). Their association to dexamethasone was assessed using the Liverpool Causality Assessment Tool. Results Forty-six children (median age, 10.2 y) were eligible for analysis. The most frequent AEs attributable to dexamethasone (Liverpool Causality Assessment Tool category of probable or definite) were hyperglycemia (63%; CTCAE v4.03 grade 3: 2%), hypertension (52%; CTCAE v4.03 grade 3: 15%), and bradycardia (46%; CTCAE v4.03 grade 3: 0%). Other AEs included dyspepsia or gastroesophageal reflux disease (24%) and alterations in mood and behavior (9%). No AE exceeded CTCAE v4.03 grade 3 in severity. Conclusions In children undergoing HSCT who received dexamethasone for CINV prophylaxis, immediate AEs attributable to dexamethasone were most often of minor clinical importance and transient.

Objectives Primary objectives were to evaluate the interrater reliability and validity of proxy-report Symptom Screening in Pediatrics Tool (SSPedi) in children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients. Secondary objective was to describe the interrater reliability of each SSPedi item. Methods Respondents were children aged eight to 18 years with cancer or HSCT recipients, and their parents or guardians. We enrolled two pediatric respondent groups. The more symptomatic group was receiving active treatment for cancer, admitted to hospital, and expected to be in a hospital three days later. The less symptomatic group either was in maintenance therapy for acute lymphoblastic leukemia or had completed cancer treatments. Convergent validity was evaluated by comparing proxy-reported mucositis, nausea and vomiting, pain, and total SSPedi scores, with child self-reported validated scales, and we hypothesized fair correlations. Discriminant validity was evaluated by comparing proxy-reported total SSPedi scores between groups. Interrater reliability of each SSPedi item was evaluated. Results Four hundred thirty-nine child and parent or guardian pairs were recruited. Mean difference in proxy-reported SSPedi scores between the more and less symptomatic groups was 8.2, 95% CI 6.6–9.8. All hypothesized relationships among measures were observed. Intraclass correlation coefficients for SSPedi items ranged from 0.34 (problems with thinking) to 0.80 (diarrhea). Conclusion Proxy-report SSPedi is reliable and valid in children aged 8 years to 18 years with cancer and HSCT recipients. Future work should support proxy-reported symptom assessment in clinical settings where children are not able to self-report or communicate bothersome symptoms.

We undertook this retrospective study to describe decisions made following asparaginase activity monitoring implementation at our center. Clinically apparent reactions (CARs) and asparaginase activity monitoring costs were described. Patients with acute lymphoblastic leukemia, aged

Traditionally in hematopoietic stem cell transplant (HSCT), cyclosporine doses are individualized using cyclosporine trough concentrations (C0) while area under the concentration vs time curve (AUC...

Background The objective was to evaluate the reliability and validity of the self-report Symptom Screening in Pediatrics Tool (SSPedi) from the perspective of children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients. Methods In this multicenter study, respondents were children age eight to 18 years who had cancer or had received HSCT, and their parents. Two different child respondent populations were targeted. More symptomatic respondents were receiving active treatment for cancer, admitted to the hospital, and expected to be in the hospital three days later. Less symptomatic respondents were in maintenance therapy for acute lymphoblastic leukemia or had completed cancer therapy. Children completed SSPedi and then responded to validated self-report measures of mucositis, nausea, pain, and global quality of life. Children in the more symptomatic group repeated SSPedi and a global symptom change scale three days later. Parent proxy-report was optional. Reliability was evaluated using intraclass correlations while convergent validity was evaluated using Spearman correlations. Results Of 502 children enrolled, 302 were in the more symptomatic group and 200 were in the less symptomatic group. Intraclass correlation coefficients were 0.88 (95% confidence interval [CI] = 0.82 to 0.92) for test-retest reliability and 0.76 (95% CI = 0.71 to 0.80) for inter-rater reliability. The mean difference in SSPedi scores between more and less symptomatic groups was 7.8 (95% CI = 6.4 to 9.2). SSPedi was responsive to change in global symptoms. All hypothesized relationships among measures were observed. Conclusions SSPedi is a self-report symptom bother tool for children with cancer and HSCT recipients that is reliable, valid, and responsive to change. SSPedi can be used for clinical and research purposes. Future work should focus on integration into care delivery.

ObjectivesTaste changes are common among paediatric patients receiving cancer treatments although specific descriptions and associations are uncertain. Primary objective was to describe the number of paediatric patients receiving cancer therapies who experienced taste changes, its impact on food intake and enjoyment of eating, and coping strategies.MethodsThis was a cross-sectional study that included English-speaking paediatric patients aged 4–18 years with a diagnosis of cancer or haematopoietic stem cell transplantation recipients receiving active treatment. Using a structured interview, we asked participants about their experience with taste changes, impacts and coping strategies. The respondent was the paediatric patient.ResultsWe enrolled 108 patients; median age was 11 years (IQR 8–15). The taste changes reported yesterday or today were food tasting bland (34%), bad (31%), different (27%), bitter (25%), extreme (19%), metallic (15%) or sour (12%). Taste changes were associated with decreased food intake (31%) and decreased enjoyment in eating (25%) yesterday or today. The most common coping strategies were eating food they liked (42%), eating strong-tasting food (39%), drinking liquids (35%), brushing teeth (31%) and sucking on candy (25%). Factors significantly associated with food tasting bad were as follows: older age (p=0.003), shorter time since cancer diagnosis (p=0.027), nausea and vomiting (p=0.008) and mucositis (p=0.009).ConclusionsAmong paediatric patients receiving cancer treatments, taste changes were common and were associated with decreased food intake and enjoyment in eating. Common coping strategies were described. Reducing nausea, vomiting and mucositis may improve taste changes.

ObjectivesTo translate a symptom screening tool developed for paediatric patients receiving cancer therapies called Symptom Screening in Pediatrics Tool (SSPedi) into Argentinian Spanish and to evaluate the understandability and cultural relevance of the translated version of SSPedi among children with cancer and paediatric haematopoietic stem cell transplant (HSCT) recipients.MethodsWe conducted a multiphase, descriptive study to translate SSPedi into Argentinian Spanish. Using two translators, forward and backward translations were performed. The translated version was evaluated by Spanish-speaking paediatric patients 8–18 years of age receiving cancer treatments in two centres in Argentina and El Salvador.Primary and secondary outcome measuresThe primary outcome was patient self-reported difficulty with understanding of the SSPedi instructions and each symptom using a 5-point Likert scale. Secondary outcomes were incorrect understanding of the SSPedi instructions, symptoms and response scale determined by cognitive interviews with the patients and rated using a 4-point Likert scale. Cultural relevance was assessed qualitatively.ResultsThere were 30 children enrolled and included in cognitive interviews; 16 lived in Argentina and 14 lived in El Salvador. The most common types of Spanish spoken were Central American (17, 57%) followed by South American (10, 33%) and Castilian (3, 10%). No changes to Argentinian Spanish SSPedi were required based on the outcomes or qualitative comments. No issues with cultural relevance were identified by any of the respondents.ConclusionsWe translated and finalised Argentinian Spanish SSPedi. Future research will focus on its use to describe bothersome symptoms by Argentinian Spanish-speaking children.

Purpose To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0–18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT). Methods The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations. Results We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children. Conclusions All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted.

To update the 2009 recommendations for the prevention of acute chemotherapy-induced emesis in children.We updated the original systematic literature search. Randomized studies were included in the evidence to support this guideline if they were primary studies fully published in full text in English or French; included only children less than 18 years old or, for mixed studies of adults and children, reported the pediatric results separately or the median or mean age was no more than 13 years; evaluated acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis; provided sufficient information to permit determination of the emetogenicity of the antineoplastic therapy administered or the study investigators stated the emetogenicity of the chemotherapy administered; included an implicit or explicit definition of complete acute CINV response; described the antiemetic regimen in full; and reported the complete acute CINV response rate as a proportion.Twenty-five randomized studies, including eight published since 2009, met the criteria for inclusion in this systematic review. Prophylaxis with a 5-HT3 antagonist (granisetron or ondansetron or palonosetron or tropisetron) +/- A dexamethasone +/- A aprepitant is recommended for children receiving highly or moderately emetogenic chemotherapy. For children receiving chemotherapy of low emetogenicity, a 5-HT3 antagonist is recommended.The findings of several randomized trials were used to update recommendations for the prevention of acute CINV. However, significant research gaps remain and must be addressed before CINV control in children can be optimized.

ObjectiveWe previously developed the paper-based Symptom Screening in Pediatrics Tool (SSPedi) designed for paediatric cancer symptom screening. Objectives were to evaluate and refine the electronic mobile application (app) of SSPedi using the opinions of children with cancer.MethodsParticipants were children 8–18 years of age with cancer. Participants completed electronic SSPedi on their own and then responded to semistructured questions to determine whether they found electronic SSPedi easy or difficult to complete and understand, understood and liked the app features (audio and animation), and understood previously difficult to understand concepts with the introduction of a help menu. After each group of 10 children, responses were reviewed to determine whether modifications were required.Results20 children evaluated electronic SSPedi. None found electronic SSPedi difficult to complete or understand. All children understood the app features and each of the 4 more difficult to understand concepts after using the help menu. 19 of 20 children thought the app was a good way to communicate with doctors and nurses.ConclusionsWe finalised an electronic version of SSPedi that is easy to use and understand with features specifically designed to facilitate child self-report. Future work will evaluate the psychometric properties of electronic SSPedi.

ObjectiveTo evaluate the feasibility of a large prospective trial aimed at improving chemotherapy-induced nausea and vomiting (CINV) control in paediatric patients undergoing oral chemotherapy during acute lymphoblastic leukaemia (ALL) maintenance therapy.MethodsEnglish-speaking children, 4.0–17.99 years old and undergoing ALL maintenance treatment with an English-speaking guardian, were eligible to participate in this observational, serial, cross-sectional feasibility study. Data were collected from participants over one to three 7-day periods during months 2–3, 5–6 and 11–12 of ALL maintenance treatment. A future trial was considered feasible if the mean time to enrol 10 patients in each of three data collection periods was ≤1 year with ≥80% of patients returning evaluable data. CINV control was described as a secondary endpoint.ResultsTwenty-nine of 31 consenting patients (median age: 6.5 years, IQR: 5.1–9.2) completed the study: 10 in months 2–3, 10 in months 5–6 and 9 in months 11–12. The total time to recruit 29 patients was 1.2 years. In each of the three data collections periods, 72% of the patients provided evaluable data. Complete CINV control was reported in 6/21 (29%) evaluable study periods.ConclusionsA future trial to evaluate interventions to improve CINV control in patients with ALL undergoing oral maintenance chemotherapy as designed in this study is not feasible. An electronic data capture method and deferring patient recruitment until the mid-maintenance to late-maintenance phase should be considered in the design of a future trial.

Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.

Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web-based application that enables symptom screening and access to clinical practice guidelines for symptom management. Objective was to determine the feasibility of a randomized trial of daily symptom screening for 5 days among children receiving cancer treatments. We included English-speaking pediatric cancer and hematopoietic stem cell transplantation (HSCT) patients who were 8–18 years of age at enrollment and who were expected to be in the hospital or in clinic daily for five consecutive days. We randomized children to either undergo daily symptom screening with symptom reports provided to the healthcare team using the SPARK vs. standard of care. The primary endpoint was feasibility, defined as being able to enroll at least 30 participants within 1 year, and among those randomized to intervention, at least 75% completing symptom screening on at least 60% of on-study days. From July 2018 to November 2018, we enrolled and randomized 30 participants. The median age at enrollment was 12.5 (range 8–18) years. Among the intervention group, the median number of days Symptom Screening in Pediatrics Tool (SSPedi) was completed at least once was 5 (range 4 to 5), with one participant missing 1 day of symptom screening. Among all participants, baseline and day 5 SSPedi scores were obtained in 29/30 participants. A randomized trial of the SPARK with daily symptom screening for 5 days was feasible. It is now appropriate to proceed toward a definitive multi-center trial to test the efficacy of SPARK to improve symptom control.

Terms used to label types of clinical recommendations and guidance are applied inconsistently and do not reflect the methods used to create each type. Here, the international Pediatric Oncology Supportive Care Guideline Network proposes a lexicon for types of recommendations and guidance documents. A lexicon describing three types of recommendations (clinical practice guideline-derived, good practice statement, and expert opinion statement) and two types of guidance documents (clinical practice guideline and expert opinion) is presented. Consistent use of this lexicon will allow pediatric oncology clinicians to readily appreciate the methods used to create clinical guidance.

Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.

Busulfan therapeutic drug monitoring (TDM) is often used to achieve target plasma exposures. Variability in busulfan plasma exposure units (BPEU) is a potential source for misinterpretation of publications and protocols and is a barrier to data capture by hematopoietic cell transplantation (HCT) registry databases. We sought to harmonize to a single BPEU for international use. Using Delphi consensus methodology, iterative surveys were sent to an increasing number of relevant clinical stakeholders. In survey 1, 14 stakeholders were asked to identify ideal properties of a BPEU. In survey 2, 52 stakeholders were asked (1) to evaluate BPEU candidates according to ideal BPEU properties established by survey 1 and local position statements for TDM and (2) to identify potential facilitators and barriers to adoption of the harmonized BPEU. The most frequently used BPEU identified, in descending order, were area under the curve (AUC) in μM × min, AUC in mg × h/L, concentration at steady state (Css) in ng/mL, AUC in μM × h, and AUC in μg × h/L. All respondents conceptually agreed on the ideal properties of a BPEU and to adopt a harmonized BPEU. Respondents were equally divided between selecting AUC in μM × min versus mg × h/L for harmonization. AUC in mg × h/L was finally selected as the harmonized BPEU, because it satisfied most of the survey-determined ideal properties for the harmonized BPEU and is read easily understood in the clinical practice environment. Furthermore, 10 major professional societies have endorsed AUC in mg × h/L as the harmonized unit for reporting to HCT registry databases and for use in future protocols and publications.

Background Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web application focused on improving symptom control. It enables pediatric cancer and hematopoietic stem cell transplant (HSCT) patients to self-report and track symptoms, and allows healthcare professionals to access guidelines for symptom management. Objective was to determine the feasibility of longitudinal collection of symptom data. Methods In this longitudinal, single-armed feasibility study, respondents were children 8–18 years of age with cancer or pediatric HSCT recipients. Participants completed symptom reporting daily for 5 days. Cognitive interviews were conducted on day 5. Quantitative evaluation included SPARK ease of use and understandability of SPARK reports. Qualitative feedback on facilitators and barriers to daily symptom screening was solicited. Feasibility was defined as ≥75% of participants completing symptom screening on at least 60% of on-study days during the five-day study. Results Among the 30 children enrolled, the median number of days SSPedi was completed at least once was 5 (range 3 to 5). Overall, 28/29 (96.6%) thought completing symptom screening using SPARK was easy or very easy. All participants understood SPARK symptom reports. Severe symptoms was the most common barrier to daily reporting while an alarm reminder system was the most commonly identified facilitator. Conclusions Daily completion of symptom screening using SPARK over 5 days was feasible in children aged 8 to 18 years with cancer and pediatric HSCT recipients. SPARK is now appropriate for use in randomized trials to evaluate the effect of symptom screening and symptom feedback.