Alberta Childhood Cancer Survivorship Research Program.

Adverse outcomes after childhood cancer have been assessed in a range of settings, but most existing studies are historical and ascertain outcomes only after 5-year survival. Here, we describe the Alberta Childhood Cancer Survivorship Research Program and its foundational retrospective, population-based cohort of Albertan residents diagnosed with a first primary neoplasm between the ages of 0 and 17 years from 1 January 2001 to 31 December 2018. The cohort was established in collaboration with the Alberta Cancer Registry and Cancer in Young People in Canada program and has been linked to existing administrative health databases and patient-reported outcome questionnaires. The cohort comprised 2580 survivors of childhood cancer, 1379 (53.4%) of whom were 5-year survivors. Approximately 48% of the cohort was female, 47% of the cohort was diagnosed between 0 and 4 years of age, and the most frequent diagnoses were leukemias (25.4%), central nervous system tumors (24.0%), and lymphomas (14.9%). Detailed treatment information was available for 1741 survivors (67.5%), with manual abstraction ongoing for those with missing data. By the study exit date, the median time since diagnosis was 5.5 years overall and 10.4 years for 5-year survivors. During the follow-up time, 82 subsequent primary cancers were diagnosed, 20,355 inpatient and 555,425 ambulatory/outpatient events occurred, 606,773 claims were reported, and 437 survivors died. The results from this research program seek to inform and improve clinical care and reduce cancer-related sequelae via tertiary prevention strategies.

Comparative Effectiveness of Pediatric Integrative Medicine: A Pragmatic Cluster-Controlled Trial.

Symptoms of pain, nausea/vomiting, and anxiety (PNVA) are highly prevalent in pediatric inpatients. Poorly managed symptoms can lead to decreased compliance with care, and prolonged recovery times. Pharmacotherapy used to manage PNVA symptoms is of variable effectiveness and carries safety risks. Complementary therapies to manage these symptoms are gaining popularity due to their perceived benefits and low risk of harm. Pediatric integrative medicine (PIM) is the combination of complementary therapies with conventional medicine in pediatric populations. A two-arm, cluster-controlled, pragmatic clinical trial was carried out to compare the effectiveness of a PIM service in conjunction with usual care, versus usual care only to treat PNVA symptoms in hospitalized pediatric patients. The primary outcome was the improvement of PNVA symptom severity using a 10-point numerical rating scale. Participant enrollment occurred between January 2013 and January 2016. A total of 872 participants (usual care n = 497; PIM n = 375) were enrolled. The PIM therapies significantly reduced PNVA symptom severity (p < 0.001). This study found that a hospital-based PIM service is both safe and effective for alleviating PNVA symptoms. Future research should carry out this work in other pediatric inpatient divisions, and in other sites to determine the reproducibility of findings.

Observational Study of Pediatric Inpatient Pain, Nausea/Vomiting and Anxiety.

Background: The prevalence and severity of pain, nausea/vomiting, and anxiety (PNVA) among hospitalized children is not well established. We describe the prevalence and severity of PNVA among hospitalized patients from oncology, general pediatrics, and cardiology services in a tertiary care center. Methods: Patients were recruited on admission and enrolled if their caregiver consented, spoke English, and were anticipated to stay 2-30 days. Symptoms were measured weekdays using age-validated tools. PNVA symptoms were described and compared. Results: We enrolled 496 (49.4%) patients of 1005 admitted. Patients were predominantly Caucasian (57.9%) on their first admission (53.6%). The average (SD) age was 8.6 years (5.9) in oncology, 4.2 (5.3) in general pediatrics and 2.6 (4.0) in cardiology. 325 (65.6%) patients reported anxiety, 275 (55.4%) reported nausea and 256 (52.0%) reported pain. Mean (SD) severity out of 10 was 3.7 (2.5) for anxiety, 3.2 (2.1) for nausea and 3.0 (1.5) for pain. Prevalence of PNVA was no different between clinical programs, but pain (p = 0.008) and nausea (p = 0.006) severity were. PNVA symptom co-occurrence was positively correlated (p < 0.001). Conclusions: Anxiety was the most common and severe symptom for hospitalized children. Patients in oncology demonstrated the least severe pain and nausea with no difference in anxiety between services.

Comparative effectiveness of pediatric integrative medicine as an adjunct to usual care for pediatric inpatients of a North American tertiary care centre: A study protocol for a pragmatic cluster controlled trial.

BACKGROUND: Some pediatric tertiary care centres in North America supplement conventional care with complementary therapies, together known as pediatric integrative medicine (PIM). Evidence to support the safety and efficacy of PIM is emerging, but the cost-effectiveness of an inpatient PIM service has yet to be assessed. METHODS/DESIGN: This study is a pragmatic cluster controlled clinical trial. Usual care will be compared to usual care augmented with PIM in three pediatric divisions; oncology, general medicine, and cardiology at one large urban tertiary care Canadian Children's Hospital. The primary outcome of the feasibility study is enrolment; the primary outcome of the main study is cost-effectiveness. Other secondary outcomes include the prevalence and severity of key symptoms (i.e. pain, nausea/vomiting and anxiety), efficacy of PIM interventions, patient safety, and parent satisfaction. DISCUSSION: This trial will be the first to evaluate the comparative effectiveness, both clinical and cost, of a PIM inpatient service. The evidence from this study will be useful to families, clinicians and decision makers, and will describe the clinical and economic value of PIM services for pediatric patients admitted to hospital.

Corrigendum to "Comparative effectiveness of pediatric integrative medicine as an adjunct to usual care for pediatric inpatients of a North American tertiary care centre: A study protocol for a pragmatic cluster controlled trial" [Contemp. Clin. Trials Commun. (2017) 12-18].

[This corrects the article DOI: 10.1016/j.conctc.2016.11.002.].

Age at cancer diagnosis, non-O blood group and asparaginase therapy are independently associated with deep venous thrombosis in pediatric oncology patients: A risk model.

INTRODUCTION: Pediatric oncology patients are at increased risk for deep venous thrombosis (DVT). Determining the sub-population of children at increased DVT risk is critical for optimum clinical management. Therefore, the aim of the current study was to identify clinical risk factors for DVT which are easily identifiable at cancer diagnosis. MATERIALS AND METHODS: A Canadian multicenter case control study in survivors of childhood cancer. Survivors who had DVT (Cases) while being treated for pediatric cancer where matched by center with a minimum of two survivors who did not experience DVT (Controls). Clinical information including age at diagnosis, type of cancer and chemotherapy were collected. Genotyping of blood group was done by single nucleotide polymorphisms analysis. RESULTS: 218 subjects were recruited at 4 Canadian pediatric centers. Multivariable analysis demonstrated 3 significant variables (reported as Odds Ratio (OR), (95% CI), p value): age at diagnosis p<0.001, non-O blood group OR 2.6 (1.3-5.2) p=0.005 and asparaginase treatment OR 2.4 (1.2-4.8) p=0.011. In order to optimise clinical utility, we reanalysed the study data with age at diagnosis categorised into four subgroups 0-≤2years, >2-≤7years, >7≤10years, >10years. A significant association with DVT were seen in children 0-≤2years (OR 3.1 (1.1-8.3) p=0.026) and >10years (OR 3.8, 1.7-8.5 p=0.001). Significant associations with DVT remained for non-O blood group, OR 2.2 (1.2-4.4) p=0.016 and asparaginase treatment, OR 2.1 (1.1-4.0) p=0.027. The value for the clinical risk model receiver operating characteristics curve was 0.67. CONCLUSIONS: We have shown 3 independent risk factors for DVT in childhood cancer.

Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy.

BACKGROUND: Childhood cancer survivors show evidence of diffuse myocardial fibrosis that is related to exercise capacity. The mechanism of reduced exercise tolerance in anthracycline cardiotoxicity remains unclear. We explored the determinants of exercise intolerance by evaluating left ventricular (LV) distensibility and functional reserve. METHODS: Patients (n = 22) and healthy controls (n = 10) underwent two-dimensional echocardiography while supine, upright, and during cycle exercise. LV distensibility was measured as the change in end-diastolic cavity area (EDCA) from supine to the upright position. LV functional reserve was assessed during peak exercise, and measured as the exercise-induced change in systolic circumferential strain rate (SR) and early-diastolic SR (EDSR). The peak rate of oxygen consumption was measured by indirect calorimetry. RESULTS: Median age of patients was 16 years (range 8-19) and controls 14 years (range 8-19). Median time since anthracycline therapy was 6 years (range 2-16). Peak oxygen consumption was significantly lower in patients compared to controls (35 ml/kg/min [28-60] vs. 45 ml/kg/min [44-53], P = 0.005). Transitioning from the supine position to the upright position caused a similar reduction in LV EDCA, suggesting similar LV distensibility between patients (-22% [-46 to -4]) and controls (-20% [-46 to -3], P = 0.3). However, during exercise, both systolic SR and EDSR reserve were significantly impaired in patients (∆SR: 93% [14-308], ∆EDSR: -4.5% [-88 to 121]) compared to controls (∆SR: 128% [54-230], P = 0.046; ∆EDSR: 74% [22-234], P = 0.02). CONCLUSIONS: Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility.

Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling.

BACKGROUND: The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors. METHODS: Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO(2)). CMR measured ventricular function, mass, T(1) and T(2) values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography. RESULTS: Patients had normal LVEF (59 ± 7%) but peak VO(2) was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = -0.49). Increased ECV correlated with decreased mass/volume ratio (r = -0.64), decreased LV wall thickness/height ratio (r = -0.72), lower peak VO(2)(r = -0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO(2) or cumulative dose. CONCLUSIONS: Myocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.