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).
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.
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.
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.
Objectives were to build a machine learning algorithm to identify bloodstream infection (BSI) among pediatric patients with cancer and hematopoietic stem cell transplantation (HSCT) recipients, and ...to compare this approach with presence of neutropenia to identify BSI.
We included patients 0-18 years of age at cancer diagnosis or HSCT between January 2009 and November 2018. Eligible blood cultures were those with no previous blood culture (regardless of result) within 7 days. The primary outcome was BSI. Four machine learning algorithms were used: elastic net, support vector machine and two implementations of gradient boosting machine (GBM and XGBoost). Model training and evaluation were performed using temporally disjoint training (60%), validation (20%) and test (20%) sets. The best model was compared to neutropenia alone in the test set.
Of 11,183 eligible blood cultures, 624 (5.6%) were positive. The best model in the validation set was GBM, which achieved an area-under-the-receiver-operator-curve (AUROC) of 0.74 in the test set. Among the 2236 in the test set, the number of false positives and specificity of GBM vs. neutropenia were 508 vs. 592 and 0.76 vs. 0.72 respectively. Among 139 test set BSIs, six (4.3%) non-neutropenic patients were identified by GBM. All received antibiotics prior to culture result availability.
We developed a machine learning algorithm to classify BSI. GBM achieved an AUROC of 0.74 and identified 4.3% additional true cases in the test set. The machine learning algorithm did not perform substantially better than using presence of neutropenia alone to predict BSI.
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.
...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.
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).
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.
This clinical practice guideline (CPG) provides clinicians with recommendations regarding chemotherapy emetogenicity classification in pediatric oncology patients. This information is critically ...important for the appropriate selection of antiemetic prophylaxis. Recommendations are based on a systematic review limited to pediatric patients and a framework for classification when antiemetic prophylaxis is provided. Findings of 87 publications informed the emetogenicity classification of 49 single‐agent and 13 combination‐agent regimens. Information required for the classification of many chemotherapies commonly administered to pediatric patients is lacking. In the absence of pediatric data, consultation of methodologically sound CPGs aimed at adult oncology patients may be appropriate.
Posaconazole (POS) is a potent triazole antifungal agent approved in adults for treatment and prophylaxis of invasive fungal infections (IFIs). The objectives of this study were to evaluate the ...pharmacokinetics (PK), safety, and tolerability of POS oral suspension in pediatric subjects with neutropenia.
This was a prospective, multicenter, sequential dose-escalation study. Enrolled subjects were divided into 3 age groups: AG1, 7 to <18 years; AG2, 2 to <7 years; and AG3, 3 months to <2 years. AG1 and AG2 were divided into 3 dosage cohorts: DC1, 12 mg/kg/day divided twice daily (BID); DC2, 18 mg/kg/day BID; and DC3, 18 mg/kg/day divided thrice daily (TID). AG3 was also divided into DC1 and DC2; however, no subjects were enrolled in DC2. Subjects received 7-28 days of POS oral suspension. PK samples were collected at predefined time points. The POS PK target was predefined as ~90% of subjects with Cavg (AUC /dosing interval) between 500 and 2500 ng/mL, with an anticipated mean steady state Cavg exposure of ~1200 ng/mL.
The percentage of subjects meeting the PK target was <90% across all age groups and dosage cohorts (range: 31% to 80%). The percentage of subjects that achieved the Cavg target of 500 to 2500 ng/mL on Day 7 ranged from 31% to 80%, with the lowest proportion in subjects 2 to <7 years receiving 12 mg/kg/day BID (AG2/DC1) and the highest proportion in subjects 7 to <18 years receiving 18 mg/kg/day TID (AG1/DC3). At all three dose levels (12 mg/kg/day BID, 18 mg/kg/day BID and 18 mg/kg/day TID), subjects in AG1 (7 to <18 years old) had higher mean PK exposures at steady state than those in AG2. High variability in exposures was observed in all groups. POS oral suspension was generally well tolerated and most of the reported adverse events were related to the subjects' underlying diseases.
The POS PK target of 90% of subjects with Cavg between 500 and 2500 ng/mL was not achieved in any of the age groups across the different dosage cohorts. New formulations of the molecule with a greater potential to achieve the established PK target are currently under investigation.
ClinicalTrials.gov identifier: NCT01716234.
Primary objective was to determine the feasibility of three times weekly symptom reporting by pediatric cancer patients for eight weeks.
We included English-speaking patients 8-18 years of age with ...cancer. Patients were sent reminders by text or email to complete Symptom Screening in Pediatrics Tool (SSPedi) three times weekly for eight weeks. When patients reported at least one severely bothersome symptom, the symptom report was emailed to the primary healthcare team. Patient-reported outcomes were obtained at baseline, week 4 ± 1 and week 8 ± 1. Symptom documentation, intervention provision for symptoms and unplanned healthcare encounters were determined by chart review at weeks 4 and 8. The primary endpoint was feasibility, defined as at least 75% patients achieving adherence with at least 60% of SSPedi evaluations. We planned to enroll successive cohorts until this threshold was met.
Two cohorts consisting of 30 patients (cohort 1 (n = 20) and cohort 2 (n = 10)) were required to meet the feasibility threshold. In cohort 1, 11/20 (55%) met the SSPedi completion threshold. Interventions applied after cohort 1 included engaging parents to facilitate pediatric patient self-report, offering mechanisms to remember username and password and highlighting potential benefits of symptom feedback to clinicians. In cohort 2, 9/10 (90%) met the SSPedi completion threshold and thus feasibility was met. Patient-reported outcomes and chart review outcomes were obtained for all participants in cohort 2.
Three times weekly symptom reporting by pediatric patients with cancer for eight weeks was feasible. Mechanisms to enhance three times weekly symptom reporting were identified and implemented. Future studies of longitudinal symptom screening can now be planned.
The National Cancer Institute (NCI) has a 40‐year history of initiatives to encourage the participation of community oncology sites into clinical trials research and clinical care. In 2014, the NCI ...re‐organized to form the NCI Community Oncology Research Program (NCORP) network across seven research bases, including the Children's Oncology Group (COG), and numerous community sites. The COG portfolio for Cancer Care Delivery Research (CCDR), mirroring the larger NCORP network, has included two studies addressing guideline congruence, as an important marker of quality cancer care, and another focusing on financial toxicity, addressing the pervasive problems of healthcare cost. CCDR is a cross‐cutting field that frequently examines intersectional aspects of healthcare delivery. With that in mind, we explicitly define domains of CCDR to propel our research agenda into the next phase of the NCORP CCDR program while acknowledging the complex and dynamic fields of clinical care, policy level decisions, research findings, and needs of communities served by the NCORP network that will inform the subsequent research questions. To ensure programmatic success, we will engage a broad interdisciplinary group of investigators and clinicians with expertise and dedication to community oncology and the populations they serve.
Gemtuzumab ozogamicin (GO), a calicheamicin-conjugated mAb against CD33, has been used in the treatment of acute myeloid leukemia (AML). We evaluated the impact of the addition of GO to standard ...chemotherapy and hematopoietic stem cell transplant (HCT) in patients withFLT3/ITD.
We analyzed children withFLT3/ITD-positive AML (n= 183) treated on two consecutive Children's Oncology Group AML trials (NCT00070174andNCT00372593). Outcomes were assessed forFLT3/ITD patients receiving standard chemotherapy with or without GO (GO vs. No-GO, respectively), and the impact of consolidation HCT for high-riskFLT3/ITD patients highFLT3/ITD allelic ratio (ITD-AR).
For allFLT3/ITD patients, complete remission (CR) rates for the GO versus No-GO cohorts were identical (64% vs. 64%;P= 0.98). Relapse rate (RR) after initial CR was 37% for GO recipients versus 59% for No-GO recipients (P= 0.02), disease-free survival (DFS) was similar (47% vs. 41%;P= 0.45), with higher treatment-related mortality (TRM) in GO recipients (16% vs. 0%;P= 0.008). Among high-riskFLT3/ITD patients with high ITD-AR, those who received HCT in first CR with prior exposure to GO had a significant reduction in RR (15% vs. 53%;P= 0.007), with a corresponding DFS of 65% versus 40% (P= 0.08), and higher TRM (19% vs. 7%;P= 0.08).
CD33 targeting with HCT consolidation may be an important therapeutic strategy in high-riskFLT3/ITD AML and its efficacy and associated toxicity warrant further investigation.
Background Symptom Screening in Pediatrics Tool (SSPedi) was developed for symptom screening by children 8-18 years. Objectives were to evaluate the reliability and validity of proxy-SSPedi and ...self-report mini-SSPedi for younger children. Methods This multi-center study enrolled guardians of children 2-7 years receiving cancer treatments (proxy-SSPedi) and their children 4-7 years (mini-SSPedi). The two populations were: (1) More symptomatic group where children were receiving active cancer treatment and were in hospital or clinic for four consecutive days; and (2) Less symptomatic group where children were receiving maintenance therapy for acute lymphoblastic leukemia or had completed cancer therapy. Proxy-SSPedi or mini-SSPedi were completed with measures of mucositis, nausea, pain, quality of life and overall symptoms. Respondents in the more symptomatic group repeated proxy-SSPedi/mini-SSPedi and a global symptom change scale 3 days later. Results There were 402 guardians and 326 children included in the analysis. Test re-test reliability of proxy-SSPedi showed intraclass correlation coefficient (ICC) 0.83 (95% confidence interval (CI) 0.72-0.90). Mean difference in proxy-SSPedi between more and less symptomatic groups was 9.7 (95% CI 8.3-11.1). Proxy-SSPedi was responsive to change and hypothesized relationships between measures were observed. With a priori threshold greater than or equai to0.6, inter-rater ICC among all dyads and those 6-7 years were 0.54 (95% CI 0.45-0.62) and 0.62 (95% CI 0.50-0.71) respectively. Among participating children, other hypothesized reliability and validity thresholds were generally met. Conclusions Proxy-SSPedi is reliable, valid and responsive in children 2-7 years old receiving cancer treatments. Mini-SSPedi can be used for children 6-7 years of age. Keywords: Symptom screening, Children, Validity, Reliability, Responsiveness, Proxy, Oncology, Hematopoietic stem cell transplantation
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