Paul Gibson

Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation.

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.

Refinement of the Symptom Screening in Pediatrics Tool (SSPedi)

Background:Objective was to evaluate and refine a new instrument for paediatric cancer symptom screening named the Symptom Screening in Pediatrics Tool (SSPedi).Methods:Respondents were children 8–18 years of age undergoing active cancer treatment and parents of eligible children. Respondents completed SSPedi once and then responded to semi-structured questions. They rated how easy or difficult SSPedi was to complete. For items containing two concepts, we asked respondents whether concepts should remain together or be separated into two questions. We also asked about each item’s importance and whether items were missing. Cognitive probing was conducted in children to evaluate their understanding of items and the response scale. After each group of 10 children and 10 parents, responses were reviewed to determine whether modifications were required. Recruitment ceased with the first group of 10 children in which modifications were not required.Results:Thirty children and 20 parents were required to achieve a final version of SSPedi. Fifteen items remain in the final version; the score ranges from 0 to 60.Conclusions:Using opinions of children with cancer and parents of paediatric cancer patients, we successfully developed a symptom screening tool that is easy to complete, is understandable and demonstrates content validity.

Classification of treatment-related mortality in children with cancer: a systematic assessment

Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause-of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (κ=0·83, 95% CI 0·60-1·00) and paediatric oncologists (0·84, 0·63-1·00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0·92, 0·78-1·00). Our approach should allow comparison of treatment-related mortality across trials and across time.

Guideline for the prevention and treatment of anticipatory nausea and vomiting due to chemotherapy in pediatric cancer patients.

This guideline provides an approach to the prevention and treatment of anticipatory chemotherapy‐induced nausea and vomiting (CINV) in children. It was developed by an international, inter‐professional panel using AGREE II methods and is based on systematic literature reviews. Evidence‐based recommendations for pharmacological and non‐pharmacological interventions to prevent and treat anticipatory CINV in children receiving antineoplastic agents are provided. Gaps in the evidence used to support the recommendations are identified. The contribution of this guideline to anticipatory CINV control in children requires prospective evaluation. Pediatr Blood Cancer 2014; 61:1506–1512.

Guideline for the prevention of acute chemotherapy‐induced nausea and vomiting in pediatric cancer patients: A focused update

This update of the 2013 clinical practice guideline provides clinicians with guidance regarding the use of aprepitant and palonosetron for the prevention of acute chemotherapy‐induced nausea and vomiting (CINV) in children. The recommendations were based on three systematic reviews. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5‐HT3 antagonists recommended for children receiving highly emetogenic chemotherapy (HEC) and the recommendation of aprepitant for children 6 months of age or older receiving HEC. To optimize CINV control in children, future work must focus on closing critical research gaps.

Guideline for the Treatment of Breakthrough and the Prevention of Refractory Chemotherapy-Induced Nausea and Vomiting in Children With Cancer

This clinical practice guideline provides an approach to the treatment of breakthrough chemotherapy‐induced nausea and vomiting (CINV) and the prevention of refractory CINV in children. It was developed by an international, interprofessional panel and is based on systematic literature reviews. Evidence‐based interventions for the treatment of breakthrough and prophylaxis of refractory CINV are recommended. Gaps in the evidence used to support the recommendations made in this clinical practice guideline were identified. The contribution of these recommendations to breakthrough and refractory CINV control in children requires prospective evaluation.

Evaluation of the electronic self-report Symptom Screening in Pediatrics Tool (SSPedi).

Objective We 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. Methods Participants 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. Results 20 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. Conclusions We 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.

Treatment with topotecan plus cyclophosphamide in children with first relapse of neuroblastoma

Reports of responses and toxicities of salvage therapies for relapsed neuroblastoma are rare and often confounded by effects of additional treatments. Our objective was to describe the outcomes and toxicities for a topotecan and cyclophosphamide (TOPO/CTX) regimen for first relapse or progression of high‐risk neuroblastoma.

Validation of the Symptom Screening in Pediatrics Tool in Children Receiving Cancer Treatments

Abstract 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.

Predictors of diagnostic interval and associations with outcome in acute lymphoblastic leukemia

Little is known about diagnostic interval lengths in childhood cancer, their predictors or impact upon survival. To date, studies have relied on questionnaires or chart abstraction. We aimed to construct and validate a diagnostic interval measure using health services data among children with acute lymphoblastic leukemia (ALL) in order to determine predictors of prolonged intervals and associations with event‐free survival (EFS).