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1.
Cancer Med ; 13(3): e7033, 2024 Feb.
Article En | MEDLINE | ID: mdl-38400668

BACKGROUND: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out-of-trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020. METHODS: Innovative therapies were defined as cancer-directed drugs used (a) off-label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines. RESULTS: We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi-targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA-mTOR-AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces. CONCLUSION: This real-world data collection illustrates an increasing use of "out-of-trial" innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies.


Antineoplastic Agents , Neoplasms , Humans , Child , Adult , Retrospective Studies , Canada , Neoplasms/drug therapy , Medical Oncology , Antineoplastic Agents/therapeutic use , Therapies, Investigational
2.
Cancer Res Commun ; 3(5): 738-754, 2023 05.
Article En | MEDLINE | ID: mdl-37377903

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer-predisposition disorder. Approximately 70% of individuals who fit the clinical definition of LFS harbor a pathogenic germline variant in the TP53 tumor suppressor gene. However, the remaining 30% of patients lack a TP53 variant and even among variant TP53 carriers, approximately 20% remain cancer-free. Understanding the variable cancer penetrance and phenotypic variability in LFS is critical to developing rational approaches to accurate, early tumor detection and risk-reduction strategies. We leveraged family-based whole-genome sequencing and DNA methylation to evaluate the germline genomes of a large, multi-institutional cohort of patients with LFS (n = 396) with variant (n = 374) or wildtype TP53 (n = 22). We identified alternative cancer-associated genetic aberrations in 8/14 wildtype TP53 carriers who developed cancer. Among variant TP53 carriers, 19/49 who developed cancer harbored a pathogenic variant in another cancer gene. Modifier variants in the WNT signaling pathway were associated with decreased cancer incidence. Furthermore, we leveraged the noncoding genome and methylome to identify inherited epimutations in genes including ASXL1, ETV6, and LEF1 that confer increased cancer risk. Using these epimutations, we built a machine learning model that can predict cancer risk in patients with LFS with an area under the receiver operator characteristic curve (AUROC) of 0.725 (0.633-0.810). Significance: Our study clarifies the genomic basis for the phenotypic variability in LFS and highlights the immense benefits of expanding genetic and epigenetic testing of patients with LFS beyond TP53. More broadly, it necessitates the dissociation of hereditary cancer syndromes as single gene disorders and emphasizes the importance of understanding these diseases in a holistic manner as opposed to through the lens of a single gene.


Li-Fraumeni Syndrome , Humans , Li-Fraumeni Syndrome/genetics , Tumor Suppressor Protein p53/genetics , Genetic Predisposition to Disease/genetics , Genes, p53 , Germ-Line Mutation/genetics
3.
J Pediatr Hematol Oncol Nurs ; 39(6): 366-378, 2022.
Article En | MEDLINE | ID: mdl-35759365

Background: There is a lack of self-management tools for adolescents with cancer (AWC). This study evaluated the feasibility of Teens Taking Charge Cancer, a web-based self-management program. Methods: A pilot randomized control trial (RCT) was conducted across 4 pediatric oncology clinics. AWC (12-18 years) and their caregivers were randomized to either the intervention or control group. All were asked to complete 12 website modules over 12 weeks (at their own pace) and received monthly calls from health coaches. The intervention website was based on cognitive behavioral principals, designed as an interactive self-guided online program, while the control consisted of education and included links to 12 general cancer websites. Outcome assessments occurred at enrollment and 12 weeks post-intervention. The primary outcomes included rate of accrual and retention, adherence to the protocol, acceptability and satisfaction with intervention using questionnaire and semi-structured interviews, adverse events and engagement with the intervention. Results: Eighty-one teen-caregiver dyads were enrolled with a retention rate of 33%. In the intervention group 46% (n = 18) logged in at least once over the 12-week period. A mean of 2.4 of 12 modules (SD 3.0) were completed; and no one completed the program. Thirty-three percent of caregivers in the intervention logged into the website at least once and none completed the full program. Discussion: The results from this pilot study suggest that the current design of the Teens Taking Charge Cancer RCT lacks feasiblity. Future web-based interventions for this group should include additional features to promote uptake and engagement with the program.


Neoplasms , Self-Management , Child , Adolescent , Humans , Pilot Projects , Surveys and Questionnaires , Neoplasms/therapy , Internet
4.
Sci Rep ; 12(1): 1404, 2022 01 26.
Article En | MEDLINE | ID: mdl-35082328

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Treatments of ALL predispose survivors to obesity, which increases the risk of cardiovascular disease and diabetes. The hallmark of obesity is excess fat mass, and adiposity is a superior predictor of cardiometabolic risk when compared to Body Mass Index (BMI), yet clinical measures of adiposity in children are lacking. The Tri-Ponderal Mass Index (TMI) (kg/m3) is a more accurate adiposity measure compared to BMI z-score in the general pediatric population. This cross-sectional study aimed to validate TMI as an adiposity measure against DEXA scan-derived adiposity, and to compare it to BMI z-score, in pediatric ALL survivors. This study was a retrospective chart review of pediatric ALL survivors diagnosed between 2004 and 2015 at McMaster Children's Hospital, a tertiary pediatric center in Ontario, Canada. One hundred and thirteen patients (Female n = 55, 48.70%) were included, and adiposity was measured using DEXA scans. Exploratory partial correlations and linear regression analyses were adjusted for age, sex, ethnicity, and ALL risk status. Both TMI and BMI z-score correlated with the DEXA-measured fat mass percentage (FM%) (partial correlation TMI versus FM% r = 0.56; p value < 0.0001; BMI z-score versus FM% r = 0.55; p value < 0.0001). In regression analyses, the association of TMI was not inferior to BMI z-score in assessing adiposity (TMI versus FM% estimated unstandardized B 0.80, 95% CI 0.56, 1.02; p value < 0.0001; BMI z-score versus FM% (unstandardized B 0.37, 95% CI 0.26, 0.49; p value < 0.0001). The TMI is a useful clinical adiposity-specific measure in survivors of pediatric ALL.


Adiposity , Antineoplastic Agents/adverse effects , Body Mass Index , Cancer Survivors , Pediatric Obesity/chemically induced , Pediatric Obesity/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Body Height , Cardiometabolic Risk Factors , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Incidence , Infant , Male , Metabolic Syndrome/chemically induced , Metabolic Syndrome/epidemiology , Ontario/epidemiology , Pediatric Obesity/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Retrospective Studies
5.
Pediatr Blood Cancer ; 68(12): e29289, 2021 12.
Article En | MEDLINE | ID: mdl-34411405

BACKGROUND: Meta-iodobenzylguanidine(MIBG) scans are used to detect neuroblastoma metastatic lesions at diagnosis and during posttreatment surveillance. MIBG positivity following induction chemotherapy correlates with poor outcome; however, there are reports of patients with progression-free survival despite MIBG positivity at the end of therapy. The factors distinguishing these survivors from patients who progress or relapse are unclear. FDG-positron-emission tomography (PET) scans can also detect metastatic lesions at diagnosis; however, their role in posttherapy surveillance is less well studied. METHODS: We performed a retrospective analysis of International Neuroblastoma Staging System (INSS) stage 4 patients to identify those with residual MIBG-avid metastatic lesions on end-of-therapy scans without prior progression. Data collected included age, disease sites, histopathology, biomarkers, treatment, imaging studies, and response. RESULTS: Eleven of 265 patients met inclusion criteria. At diagnosis three of 11 patients were classified as intermediate and eight of 11 high risk; nine of 11 had documented marrow involvement. Histologic classification was favorable for four of 10 and MYCN amplification was detected in zero of 11 cases. The median time with persistent MIBG positivity following treatment was 1.5 years. Seven patients had at least one PET scan with low or background activity. Biopsies of three of three MIBG-avid residual lesions showed differentiation. All patients remain alive with no disease progression at a median of 4.0 years since end of therapy. CONCLUSION: Persistently MIBG-avid metastatic lesions in subsets of patients following completion of therapy may not represent active disease that will progress. Further studies are needed to determine whether MYCN status or other biomarkers, and/or PET scans, may help identify patients with residual inactive MIBG lesions who require no further therapy.


Neoplasms, Second Primary , Neuroblastoma , 3-Iodobenzylguanidine , Guanidine/therapeutic use , Humans , N-Myc Proto-Oncogene Protein , Neoplasm Recurrence, Local , Neuroblastoma/drug therapy , Neuroblastoma/therapy , Positron-Emission Tomography/methods , Retrospective Studies
6.
Adolesc Health Med Ther ; 12: 9-15, 2021.
Article En | MEDLINE | ID: mdl-33727877

BACKGROUND: Obesity is characterized by the disproportionate expansion of the fat mass and is most commonly diagnosed using the Body Mass Index (BMI) z-score or percentile in children. However, these measures associate poorly with the fat mass. This is important, as adiposity is a more robust predictor of cardiometabolic risk than BMI-based measures, but there are limited clinical measures of adiposity in children. A new measure, the Tri-ponderal Mass Index (TMI, kg/m3) has recently demonstrated robust prediction of adiposity in children. The aim of this study is to explore the association of leptin, a validated biomarker of the fat mass, with TMI. METHODS: One hundred and eight children and adolescents were included in this cross-sectional study. Height and weight were used to calculate TMI. Plasma leptin was measured using ELISA. Multivariable regression analysis was applied to determine the predictors of TMI. RESULTS: The age range of participants included in this study was 8.00-16.90 years (female n=48, 44%). Leptin correlated with BMI percentile (r=0.64, p-value <0.0001) and TMI (r=0.71, p-value <0.0001). The multivariable regression analysis revealed that BMI percentile (Estimated Beta-coefficient 0.002, 95% CI 0.002-0.003, p-value <0.0001) and Leptin (Estimated Beta-coefficient 0.05, 95% CI 0.02-0.07, p-value 0.013) were associated with TMI. CONCLUSION: Leptin is associated with TMI in healthy children. The TMI is a feasible clinical measure of adiposity that may be used to stratify children and adolescents for further assessments and interventions to manage and attempt to prevent cardiometabolic comorbidities.

7.
Virchows Arch ; 478(6): 1179-1185, 2021 Jun.
Article En | MEDLINE | ID: mdl-33392797

Prevalence of discrepancies between antemortem clinical diagnoses and postmortem autopsy findings is uncertain in pediatric oncology given improving diagnostic capabilities over time. Primary objective was to describe discrepancies between antemortem and postmortem diagnosis of pediatric cancer deaths. Secondary objective was to compare clinical characteristics of deaths with and without major diagnostic discrepancies. This was a retrospective study that included pediatric cancer patients diagnosed and treated in Ontario and who died from 2003 to 2012. Antemortem clinical diagnoses associated with mortality were determined by reviewing the patient's health records 2 weeks prior to death while the postmortem diagnoses were determined by the autopsy report. Discrepancies among these diagnoses were classified using the Goldman criteria where major discrepancies were directly related to the cause of death in contrast to minor discrepancies. Among the 821 patients who died, 118 (14%) had an autopsy and were included. Of these autopsies, 12 (10%) had a major diagnostic discrepancy between antemortem and postmortem diagnoses. Major discrepancies consisted of opportunistic infections (n = 5), missed cancer diagnosis (n = 3), and organ complications (n = 4). Death in a high acuity setting (12/12, 100% vs. 60/106, 57%; P = 0.003) and treatment-related mortality (12/12, 100% vs. 60/106, 57%; P = 0.003) were significantly associated with major discrepancy. Major diagnostic discrepancy was found in 10% of pediatric oncology autopsies. Missed infections and organ complications were predominant etiologies. Death in a high acuity setting and treatment-related mortality were associated with major diagnostic discrepancies. Autopsies continue to be important for improving diagnostic insight and may improve future clinical care.


Autopsy , Cause of Death , Neoplasms/diagnosis , Neoplasms/pathology , Autopsy/methods , Diagnostic Errors , Female , Humans , Male , Medical Oncology/methods , Pediatrics , Retrospective Studies
8.
Support Care Cancer ; 29(6): 3137-3144, 2021 Jun.
Article En | MEDLINE | ID: mdl-33067767

INTRODUCTION: The objectives of this study were to describe reports of bother for feeling scared or worried among children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients, and to identify factors associated with it. METHODS: We included children receiving cancer treatments who were 8-18 years of age. Three patient types were enrolled: inpatients receiving active cancer treatment, outpatients receiving maintenance acute lymphoblastic leukemia chemotherapy, and outpatients in survivorship. Amount of bother due to feeling scared or worried yesterday or today was self-reported using the Symptom Screening in Pediatrics Tool (SSPedi) on a 0-4 scale. Risk factors were evaluated using logistic regression. RESULTS: Among the 502 children included, 225 (45.0%) reported any degree of bother (score ≥ 1) and 29 (5.8%) reported severe bother (score ≥ 3) for feeling scared or worried. In multiple regression evaluating any bother, boys were less likely to be bothered (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41-0.87) and inpatients receiving active cancer treatment were more likely to be bothered compared to outpatients in survivorship (OR 3.58, 95% CI 2.00-6.52). The only factor associated with being severely bothered by feeling scared or worried was clinic visit or admission due to fever (OR 4.57, 95% CI 1.24-13.60). DISCUSSION: We found 45% of children receiving cancer treatments reported being bothered by feeling scared or worried. Girls and inpatients receiving active treatment experienced more bother of any degree, while visiting the hospital due to fever was associated with being severely bothered. Future work should identify interventions to prevent or alleviate this symptom.


Early Detection of Cancer/methods , Neoplasms/psychology , Neoplasms/therapy , Symptom Assessment/methods , Adolescent , Child , Female , Humans , Male , Mass Screening , Pediatrics , Self Report
9.
Sci Rep ; 10(1): 18606, 2020 10 29.
Article En | MEDLINE | ID: mdl-33122755

While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin's profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) and 126 controls (n = 59 female) who were 5-17 years old were included. Partial correlations and multivariable regression analyses assessed the relationship between HMW adiponectin and adiposity. HMW adiponectin was inversely associated with total and central adiposity (FM%: ß - 0.21, 95% CI - 0.15, - 0.08; p value < 0.0001; WHR: ß - 0.14, 95% CI - 0.02, - 0.01; p value < 0.0001 ;WHtR: ß - 0.21, 95% CI - 0.05, - 0.03; p value < 0.0001). In conclusion, HMW adiponectin is inversely correlated with adiposity in SCBT. Adiponectin may serve as a biomarker of cardiometabolic risk and response to interventions to prevent and manage obesity and its comorbidities in SCBT.


Adiponectin/metabolism , Adiposity/physiology , Brain Neoplasms/metabolism , Adipokines/metabolism , Adipose Tissue/metabolism , Adolescent , Biomarkers, Tumor/metabolism , Cancer Survivors , Cardiovascular Diseases/metabolism , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Molecular Weight , Obesity/metabolism , Risk Factors
10.
Cancers (Basel) ; 12(11)2020 Oct 22.
Article En | MEDLINE | ID: mdl-33105727

Childhood obesity is a growing epidemic with numerous global health implications. Over the past few years, novel insights have emerged about the contribution of adult obesity to cancer risk, but the evidence base is far more limited in children. While pediatric patients with acute lymphoblastic leukemia (ALL) are at risk of obesity, it is unclear if there are potential causal mechanisms by which obesity leads to ALL development. This review explores the endocrine, metabolic and immune dysregulation triggered by obesity and its potential role in pediatric ALL's genesis. We describe possible mechanisms, including adipose tissue attraction and protection of lymphoblasts, and their impact on ALL chemotherapies' pharmacokinetics. We also explore the potential contribution of cytokines, growth factors, natural killer cells and adipose stem cells to ALL initiation and propagation. While there are no current definite causal links between obesity and ALL, critical questions persist as to whether the adipose tissue microenvironment and endocrine actions can play a causal role in childhood ALL, and there is a need for more research to address these questions.

11.
Sci Rep ; 10(1): 4711, 2020 03 13.
Article En | MEDLINE | ID: mdl-32170116

Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of this study was to determine if leptin levels are associated with the adipose mass in SCBT, and to define its predictors. This cross-sectional study included 74 SCBT (n = 32 females) with 126 non-cancer controls (n = 59 females). Total adiposity was measured using Bioelectrical Impendence Analysis (BIA) and central adiposity was measured using waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). We used multivariable linear regression analysis to determine if leptin predicts adiposity in SCBT and adjusted for age, sex, puberty, and cancer status. Leptin correlated strongly with total (p < 0.001) and central (WHR p = 0.001; WHtR p < 0.001) adiposity in SCBT and non-cancer controls. In conclusion, leptin is a potential biomarker for adiposity in SCBT, and further investigation is needed to clarify if leptin is a predictor of future cardiometabolic risk in SCBT.


Adiposity/genetics , Brain Neoplasms , Cancer Survivors , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/etiology , Leptin/blood , Adolescent , Biomarkers/blood , Child , Cross-Sectional Studies , Early Diagnosis , Female , Humans , Male , Predictive Value of Tests , Risk Factors , Waist-Height Ratio , Waist-Hip Ratio
12.
Cancer Metastasis Rev ; 39(1): 79-90, 2020 03.
Article En | MEDLINE | ID: mdl-31993840

Most children are surviving acute lymphoblastic leukemia (ALL) today. Yet, the emergence of cardiometabolic comorbidities in this population may impact long-term outcomes including the quality of life and lifespan. Obesity is a major driver of cardiometabolic disorders in the general population, and in ALL patients it is associated with increased risk of hypertension, dysglycemia, and febrile neutropenia when compared with lean ALL patients undergoing therapy. This systematic review aims to assess the current evidence for bariatric interventions to manage obesity in children with ALL. The primary outcome for this systematic review was the change in BMI z-score with implementation of the interventions studied. Literature searches were conducted in several databases. Ten publications addressing the study question were included in this review, and five studies were used in the meta-analysis to assess the impact of the bariatric interventions on obesity. The BMI z-score did not change significantly with the interventions. However, the quality of evidence was low, which precluded the recommendation of their use. In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL.


Diet, Reducing , Exercise , Obesity/complications , Obesity/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Bariatric Surgery , Bariatrics/methods , Child , Humans , Life Style , Obesity/surgery , Randomized Controlled Trials as Topic
13.
Adolesc Health Med Ther ; 10: 59-65, 2019.
Article En | MEDLINE | ID: mdl-31118856

Objectives: The number of children who survive cancer is reaching new record levels, thanks to improved management strategies. However, this population is predisposed to chronic health conditions including cardiovascular disease and type 2 diabetes, yet the full scale of these diagnoses in this population is unclear. This protocol describes the conduct of a systematic review to report on the prevalence of diabetes mellitus (DM) subtypes in childhood cancer survivors. Methods: Searches will be conducted in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We will also search gray literature in Theses A&I, ProQuest Dissertations, and Web of Science as well as clinicaltrials.gov. Screening search results and data abstraction will be done independently by two reviewers. We will conduct a meta-analysis if two studies have similar designs, populations, methods, and outcome measures reported. Results: The findings of this systematic review will provide insights into the scale of diabetes in childhood cancer survivors to allow the prioritization of subpopulations that need specific interventions to screen, prevent, and treat DM. This will likely lead to improved outcomes in childhood cancer survivors.

14.
Pediatr Blood Cancer ; 66(5): e27646, 2019 05.
Article En | MEDLINE | ID: mdl-30729654

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.


Antineoplastic Agents/adverse effects , Antineoplastic Agents/classification , Nausea/chemically induced , Neoplasms/drug therapy , Practice Guidelines as Topic/standards , Vomiting/chemically induced , Child , Clinical Trials as Topic , Humans , Prognosis
15.
Support Care Cancer ; 27(6): 2247-2254, 2019 Jun.
Article En | MEDLINE | ID: mdl-30324284

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.


Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/complications , Taste Disorders/etiology , Taste/physiology , Transplantation Conditioning/adverse effects , Adolescent , Child , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Male , Neoplasms/pathology , Prospective Studies , Taste Disorders/pathology , Transplantation Conditioning/methods
16.
Support Care Cancer ; 27(7): 2665-2671, 2019 Jul.
Article En | MEDLINE | ID: mdl-30478671

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Fatigue/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Child , Female , Humans , Logistic Models , Male , Risk Factors , Young Adult
17.
J Pediatric Infect Dis Soc ; 8(4): 354-357, 2019 Sep 25.
Article En | MEDLINE | ID: mdl-30165563

Among 235 children with acute myeloid leukemia, 17 experienced 19 perianal infections. Among 12 episodes with definite abscess, 75% were severely neutropenic. Sixteen diagnostic imaging evaluations were performed; diagnostic yield was similar between computerized tomography of pelvis (5 of 10) and ultrasound (3 of 5). Consistent management approaches to perianal infection should be developed.


Bacterial Infections/complications , Bacterial Infections/diagnosis , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Abscess , Adolescent , Bacterial Infections/epidemiology , Bacterial Infections/physiopathology , Canada/epidemiology , Child , Child, Preschool , Humans , Infant , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/physiopathology , Retrospective Studies
18.
BMJ Open ; 8(6): e022530, 2018 06 22.
Article En | MEDLINE | ID: mdl-29934396

INTRODUCTION: Acute lymphoblastic leukaemia is the most common paediatric cancer. Survivors of childhood acute lymphoblastic leukaemia (SALL) are at risk of obesity and related cardiometabolic diseases including type 2 diabetes, hypertension, stroke and cardiovascular events. Therefore, it is important to address obesity in this population as this may help mitigate future cardiometabolic comorbidities. In this systematic review, we aim to assess current treatment strategies including lifestyle interventions, pharmacotherapy and bariatric surgery to manage overweight and obesity in SALL. METHODS AND ANALYSIS: We will search the following databases for primary studies: CINAHL, SPORTDiscus, EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. In addition, unpublished primary studies will be searched in ClinicalTrials.gov as well as conference proceedings, presentations, abstracts, editorials and ProQuest Dissertations and Theses A&I. Reviewers will perform title, abstract, and full-text screening as well as data abstraction and risk of bias assessment independently with a third reviewer to be consulted to resolve disagreements. Searches will be run and updated through May 1st, 2018. The overall quality of the evidence will be determined using the Grading of Recommendations, Assessment, Development, and Evaluation criteria for each outcome. A meta-analysis will be performed if two studies deploying similar interventions, populations, and design and outcomes are identified. ETHICS AND DISSEMINATION: As individual patient data will not be included, we do not require ethics approval. This review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42016051031.


Obesity Management/methods , Pediatric Obesity/complications , Pediatric Obesity/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Survivors/psychology , Bariatric Surgery , Child , Exercise , Humans , Life Style , Nutrition Therapy , Pediatric Obesity/psychology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Research Design , Systematic Reviews as Topic
19.
J Pain Symptom Manage ; 56(1): 107-112, 2018 07.
Article En | MEDLINE | ID: mdl-29630923

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.


Neoplasms/diagnosis , Neoplasms/therapy , Proxy , Symptom Assessment , Adolescent , Child , Cohort Studies , Female , Hematopoietic Stem Cell Transplantation , Humans , Male , Observer Variation , Parents , Psychometrics , Symptom Assessment/methods
20.
Cancer Med ; 7(5): 1750-1755, 2018 05.
Article En | MEDLINE | ID: mdl-29573197

Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self-report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least "a little") and those who rated the degree of bother as severe ("a lot" or "extremely"). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15-18 and 11-14 years vs. 8-10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1-4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (ß = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms.


Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/diagnosis , Symptom Assessment/methods , Adolescent , Adolescent, Hospitalized , Canada , Child , Child, Hospitalized , Early Detection of Cancer , Female , Humans , Logistic Models , Male , Psychometrics , Self Report , United States
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