Primary intramedullary extradural Ewing sarcoma.

Ewing sarcoma is the second most frequent primary bone tumour of childhood and adolescence. The aim of this report is to describe the imaging, pathology, clinical findings, and treatment of a primary intradural extramedullary Ewing sarcoma with a unique intracranial metastatic component in a pediatric patient. A 14-year-old girl with a history of mood disorders presented to the emergency department with a 3-week history of neck torticollis, cervical pain, paresis, and paresthesia of the upper and lower extremities on the left side. Initially, non-organic causes such as somatization or conversion disorder were suspected. She returned 3 months later when her symptoms worsened. MRI of the head and spine was performed, and demonstrated the presence of a suprasellar, retro-chiasmatic mass lesion. There was also diffuse leptomeningeal enhancement, another well-defined intradural extramedullary lesion the sacral region and several multifocal cauda equina soft tissue nodules. The patient first underwent surgery. The patient was also treated with a combination of chemotherapy (vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE)) and radiation as per the Children's Oncology Group AEWS1221 protocol. Most recent imaging conducted 22 months after the initial mass discovery revealed improvement of the suprasellar mass lesion with residual stable appearance of the prominence and enhancement of the pituitary stalk and tuber cinereum. There was interval improvement of the spinal lesions with no convincing residual. Clinically, at almost three years since initial imaging findings, and 25 months since completing treatment, she is stable from an oncology perspective.

Quick, Effective Screening Tasks Identify Children With Medical Conditions or Disabilities Needing Physical Literacy Support.

PURPOSE: This study evaluated screening tasks able to identify children with medical conditions or disabilities who may benefit from physical literacy. METHOD: Children completed ≤20 screening tasks during their clinic visit and then the Canadian Assessment of Physical Literacy (2nd edition) at a separate visit. Total Canadian Assessment of Physical Literacy scores <30th percentile were categorized as potentially needing physical literacy support. Receiver operator characteristic curves identified assessment cut points with 80% sensitivity and 40% specificity relative to total physical literacy scores. RESULTS: 223 children (97 girls; 10.1 [2.6] y) participated. Physical activity adequacy, predilection, and physical competence achieved ≥80% sensitivity and ≥40% specificity in both data sets. Adequacy ≤ 6.5 had 86% to 100% sensitivity and 48% to 49% specificity. Daily screen time >4.9 hours combined with Adequacy ≤6.15 had 88% to 10% sensitivity and 53% to 56% specificity. CONCLUSIONS: Activity adequacy, alone or with screen time, most effectively identified children likely to benefit from physical literacy support. Adequacy and screen time questionnaires are suitable for clinical use. Similar results regardless of diagnosis suggest physical competence deficits are not primary determinants of active lifestyles. Research to enhance screening specificity is required.

Gemtuzumab Ozogamicin Monotherapy Is a Well-tolerated Palliative Chemotherapy Option in Pediatric Multiply Relapsed Acute Myeloid Leukemia: A Multicenter Case Series and Review of the Literature.

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody that is Food and Drug Administration approved in upfront acute myeloid leukemia (AML) for patients over 1-month old, and for relapsed or refractory AML in patients over 2 years old. GO is now integrated in upfront pediatric AML treatment, and often in CD33+ relapse treatment combined with intensive conventional chemotherapy. Although GO was initially tested as a monotherapeutic agent in relapsed or refractory AML, there are few data in pediatric patients supporting this indication. In this review, we report 4 cases of multiply relapsed pediatric AML patients who were treated with GO monotherapy with palliative intent. Three of 4 patients obtained a complete response with GO reinduction, either as monotherapy or paired with conventional chemotherapy. Three patients remained in remission respectively for 5, 17, and 9 months with GO continuation monotherapy. The literature was reviewed regarding the use of GO in pediatric AML relapse settings.

Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes.

BACKGROUND: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation. METHODS: This study assessed MIPOGG's performance in identifying Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin (nevoid basal cell carcinoma) syndromes in a retrospective series of 84 children diagnosed with cancer and one of these four CPSs in Canadian hospitals over an 18-year period. RESULTS: MIPOGG detected 82 of 83 (98.8%) evaluable patients with any one of these four genetic conditions and demonstrated an appropriate rationale for suggesting CPS evaluation. When compared with syndrome-specific clinical screening criteria, MIPOGG's ability to correctly identify children with any of the four CPSs was equivalent to, or outperformed, existing clinical criteria respective to each CPS. CONCLUSION: This study adds evidence that MIPOGG is an appropriate tool for CPS screening in clinical practice. MIPOGG's strength is that it starts with a specific cancer diagnosis and incorporates criteria relevant for associated CPSs, making MIPOGG a more universally accessible diagnostic adjunct that does not require in-depth knowledge of each CPS.

A Needs Assessment Survey of Division Chiefs at an Academic Children's Hospital.

Purpose: The Division Chief at an academic health sciences centre has many leadership roles and responsibilities. There are no data on leadership training needs for Division Chiefs, and so we sought to design and implement a needs assessment for pediatric Division Chiefs at CHEO, a pediatric academic health sciences centre in Eastern Ontario, Canada. Methods: A needs assessment survey was developed with the aim to document demographics, preparedness for the role of Division Chief and desired leadership training for the role. This survey was piloted, revised and then distributed to all the Division Chiefs at our institution. The results of each question were collated, and simple descriptive statistics were calculated. Results: The survey was completed by 22 of 31 Division Chiefs. The majority of respondents were from the Department of Pediatrics (63.6%), followed by Surgery (20%), Psychiatry (3.3%) and Laboratory Medicine (3.3%). Their mean length of time as Division Chief was 5.5 years. Seventy-seven percent had concurrent leadership roles in addition to the role of Division Chief. None felt they were very well prepared for the role, five felt they were somewhat well prepared, nine were neutral, five were somewhat unprepared and three were very unprepared for the role. Half of the respondents received mentoring, either formal or informal, for their role and all but one felt that formal mentoring would have been useful. In terms of desired training, the Division Chiefs felt they had the most knowledge and skills in patient safety. All wanted training in developing divisional budgets, and many desired training in supporting the academic mission of the Division. Conclusion: Overall, this needs assessment identified an unmet need for leadership training and development among Division Chiefs. The findings are being used to optimize onboarding of Division Chiefs and an ongoing leadership development program targeted at this group.

Reliability and validity of proxy-SSPedi and mini-SSPedi in pediatric patients 2-7 years receiving cancer treatments.

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 ≥0.6, 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.

Low-Dose Metronomic Topotecan and Pazopanib (TOPAZ) in Children with Relapsed or Refractory Solid Tumors: A C17 Canadian Phase I Clinical Trial.

Oral metronomic topotecan represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib in targeting angiogenesis. A phase I and pharmacokinetic (PK) study of this combination was performed in children with relapsed/refractory solid tumors. Oral topotecan and pazopanib were each administered daily without interruption in 28-day cycles at five dose levels (0.12 to 0.3 mg/m2 topotecan and 125 to 160 mg/m2 pazopanib powder for oral suspension (PfOS)), with dose escalation in accordance with the rolling-six design. PK studies were performed on day 1 and at steady state. Thirty patients were enrolled, with 26 evaluable for dose-limiting toxicity (DLT), with median age 12 years (3-20). Toxicities were generally mild; the most common grade 3/4 adverse events related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphopenia (11%), AST elevation (11%), and lipase elevation (11%). Only two cycle 1 DLTs were observed on study, both at the 0.3/160 mg/m2 dose level comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle 1 required treatment discontinuation. The best response was stable disease in 10/25 patients (40%) for a median duration of 6.4 (1.7-45.1) months. The combination of oral metronomic topotecan and pazopanib is safe and tolerable in pediatric patients with solid tumors, with a recommended phase 2 dose of 0.22 mg/m2 topotecan and 160 mg/m2 pazopanib. No objective responses were observed in this heavily pre-treated patient population, although 40% did achieve stable disease for a median of 6 months. While this combination is likely of limited benefit for relapsed disease, it may play a role in the maintenance setting.

A Pilot Randomized Control Trial of Teens Taking Charge: A Web-based Self-management Program for Adolescents with Cancer.

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.

The expense of sending cerebrospinal fluid for analysis on all lumbar punctures in pediatric acute lymphoblastic leukemia patients.

BACKGROUND: Central nervous system (CNS) relapse in pediatric acute lymphoblastic leukemia (ALL) patients is uncommon. The cerebrospinal fluid (CSF) of patients with ALL is routinely sampled at each intrathecal chemotherapy treatment to screen for CNS relapse. The analysis of CSF is both time consuming and resource intensive and must be completed approximately 20 times per patient throughout treatment. Our objective was to examine the expense of routine screening on all CSF samples for CNS relapse in ALL patients, and to identify if CNS relapse can be detected clinically. METHODS: We identified all patients diagnosed with ALL at the Children's Hospital of Eastern Ontario (CHEO) between January 2001 and June 2021. We collected the total number of CSF samples in these patients and the number of CSF samples positive for CNS relapse. An in-depth chart review on the patients who relapsed in the CNS was completed to identify symptoms at relapse. RESULTS: Over the study period, 351 patients were diagnosed with ALL and underwent a total of 6515 lumbar punctures (LPs), each of which examined the CSF. The cost of CSF sample analysis is $14.32 (Canadian dollars [CDN]); thus, the total cost for the study sample was $93,294.80 (CDN). There were 14 CNS relapses and although symptoms including headache, vomiting, and fatigue were common, two patients were asymptomatic at relapse. CONCLUSIONS: Given the marginal cost of routine CSF screening and the lack of specific and sensitive symptoms for CNS relapse, we conclude that the routine practice of sending all CSF samples for analysis of CNS relapse in ALL patients is relatively inexpensive and beneficial.

Treatment of Sinusoidal Obstruction Syndrome With Defibrotide in Pediatric Cancer Patients Following Nontransplant-associated Chemotherapy: A Case Report and Review of the Literature.

Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.

Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for Identifying Cancer Predisposition Syndromes.

IMPORTANCE: Prompt recognition of a child with a cancer predisposition syndrome (CPS) has implications for cancer management, surveillance, genetic counseling, and cascade testing of relatives. Diagnosis of CPS requires practitioner expertise, access to genetic testing, and test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading to missed CPS diagnoses. Advances in electronic health technology can facilitate CPS risk assessment. OBJECTIVE: To evaluate the diagnostic accuracy of a CPS prediction tool (McGill Interactive Pediatric OncoGenetic Guidelines [MIPOGG]) in identifying children with cancer who have a low or high likelihood of having a CPS. DESIGN, SETTING, AND PARTICIPANTS: In this international, multicenter diagnostic accuracy study, 1071 pediatric (<19 years of age) oncology patients who had a confirmed CPS (12 oncology referral centers) or who underwent germline DNA sequencing through precision medicine programs (6 centers) from January 1, 2000, to July 31, 2020, were studied. EXPOSURES: Exposures were MIPOGG application in patients with cancer and a confirmed CPS (diagnosed through routine clinical care; n = 413) in phase 1 and MIPOGG application in patients with cancer who underwent germline DNA sequencing (n = 658) in phase 2. Study phases did not overlap. Data analysts were blinded to genetic test results. MAIN OUTCOMES AND MEASURES: The performance of MIPOGG in CPS recognition was compared with that of routine clinical care, including identifying a CPS earlier than practitioners. The tool's test characteristics were calculated using next-generation germline DNA sequencing as the comparator. RESULTS: In phase 1, a total of 413 patients with cancer (median age, 3.0 years; range, 0-18 years) and a confirmed CPS were identified. MIPOGG correctly recognized 410 of 412 patients (99.5%) as requiring referral for CPS evaluation at the time of primary cancer diagnosis. Nine patients diagnosed with a CPS by a practitioner after their second malignant tumor were detected by MIPOGG using information available at the time of the first cancer. In phase 2, of 658 children with cancer (median age, 6.6 years; range, 0-18.8 years) who underwent comprehensive germline DNA sequencing, 636 had sufficient information for MIPOGG application. When compared with germline DNA sequencing for CPS detection, the MIPOGG test characteristics for pediatric-onset CPSs were as follows: sensitivity, 90.7%; specificity, 60.5%; positive predictive value, 17.6%; and negative predictive value, 98.6%. Tumor DNA sequencing data confirmed the MIPOGG recommendation for CPS evaluation in 20 of 22 patients with established cancer-CPS associations. CONCLUSIONS AND RELEVANCE: In this diagnostic study, MIPOGG exhibited a favorable accuracy profile for CPS screening and reduced time to CPS recognition. These findings suggest that MIPOGG implementation could standardize and rationalize recommendations for CPS evaluation in children with cancer.

Utility of a Cancer Predisposition Screening Tool for Predicting Subsequent Malignant Neoplasms in Childhood Cancer Survivors.

PURPOSE: Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation. We evaluated MIPOGG's ability to predict SMN development in CCS. METHODS: Using the provincial cancer registry (Ontario, Canada), and adopting a nested case-control approach, we identified CCS diagnosed and/or treated for a primary malignancy before age 18 years (1986-2015). CCS who developed an SMN (cases) were matched, by primary cancer and year of diagnosis, with CCS who did not develop an SMN (controls) over the same period (1:5 ratio). Potential predictors for SMN development (chemotherapy, radiation, and MIPOGG output) were applied retrospectively using clinical data pertaining to the first malignancy. Conditional logistic regression models estimated hazard ratios and 95% CIs associated with each covariate, alone and in combination, for SMN development. RESULTS: Of 13,367 children with a primary cancer, 317 (2.4%) developed an SMN and were matched to 1,569 controls. A MIPOGG output recommending evaluation was significantly associated with SMN development (hazard ratio 1.53; 95% CI, 1.06 to 2.19) in a multivariable model that included primary cancer therapy exposures. MIPOGG was predictive of SMN development, showing value in nonhematologic malignancies and in CCS not exposed to radiation. CONCLUSION: MIPOGG has additional value for SMN prediction beyond treatment exposures and may be beneficial in decision making for enhanced individualized SMN surveillance strategies for CCS.

Home-Based Pediatric Cancer Care: Perspectives and Improvement Suggestions From Children, Family Caregivers, and Clinicians.

PURPOSE: Although the hospital remains the dominant site for delivering most pediatric cancer care, home-based care is increasingly provided. To effectively deliver comprehensive, relevant, and acceptable care in children's homes, the voices of these key informants must be considered. We examined the views of children with cancer, their family caregivers, and clinicians on home-based cancer care to identify necessary strategies to improve the delivery of care. METHODS: Children with cancer, their family caregivers, and multiprofessional clinicians who provide care at a tertiary pediatric care center or in the community participated in audio-recorded, semistructured interviews in French and English. Interviews were conducted until data saturation in each participant group was achieved. Interviews were transcribed, coded, and analyzed using thematic analysis. RESULTS: Thirteen children, 20 family caregivers, and 22 clinicians participated. Home-based care was endorsed as a means to improve child health-, family social- and financial-, and system-level outcomes. The success of a home-based model is built on care that addresses child and family informational, treatment and care, material, and psychosocial needs. Mechanisms to improve care include enhanced homecare agency-hospital-family communication, training for homecare nurses in pediatric cancer care, virtual solutions, and an expanded breadth of services provided in-home. Child-, family-, and system-related factors affect the delivery of optimal home-based care. CONCLUSION: Children, families, and clinicians value a model of pediatric cancer care that incorporates home-based services. The insights of these key informants should be reflected in the principles that become the basis of home-based cancer care best practices.

Characterization of physical literacy in children with chronic medical conditions compared with healthy controls: a cross-sectional study.

To determine the physical literacy, defined as the capability for a physically active lifestyle, of children with medical conditions compared with healthy peers, this multicenter cross-sectional study recruited children with medical conditions from cardiology, neurology (including concussion), rheumatology, mental health, respirology, oncology, hematology, and rehabilitation (including cerebral palsy) clinics. Participants aged 8-12 years (N = 130; mean age: 10.0 ± 1.44 years; 44% female) were randomly matched to 3 healthy peers from a normative database, based on age, gender, and month of testing. Total physical literacy was assessed by the Canadian Assessment of Physical Literacy, a validated assessment of physical literacy measuring physical competence, daily behaviour, knowledge/understanding, and motivation/confidence. Total physical literacy mean scores (/100) did not differ (t(498) = -0.67; p = 0.44) between participants (61.0 ± 14.2) and matched healthy peers (62.0 ± 10.7). Children with medical conditions had lower mean physical competence scores (/30; -6.5 [-7.44 to -5.51]; p < 0.001) but higher mean motivation/confidence scores (/30; 2.6 [1.67 to 3.63]; p < 0.001). Mean daily behaviour and knowledge/understanding scores did not differ from matches (/30; 1.8 [0.26 to 3.33]; p = 0.02;/10; -0.04 [-0.38 to 0.30]; p = 0.81; respectively). Children with medical conditions are motivated to be physically active but demonstrate impaired movement skills and fitness, suggesting the need for targeted interventions to improve their physical competence. Novelty: Physical literacy in children with diverse chronic medical conditions is similar to healthy peers. Children with medical conditions have lower physical competence than healthy peers, but higher motivation and confidence. Physical competence (motor skill, fitness) interventions, rather than motivation or education, are needed for these youth.

Leptin is Associated with the Tri-Ponderal Mass Index in Children: A Cross-Sectional Study.

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.

Diagnostic discrepancies between antemortem clinical diagnosis and autopsy findings in pediatric cancer patients.

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.

Feeling scared or worried self-report in children receiving cancer treatments using the Symptom Screening in Pediatrics Tool (SSPedi).

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.

High molecular weight adiponectin levels are inversely associated with adiposity in pediatric brain tumor survivors.

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.

Pontine gliomas a 10-year population-based study: a report from The Canadian Paediatric Brain Tumour Consortium (CPBTC).

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG) are midline gliomas that arise from the pons and the majority are lethal within a few months after diagnosis. Due to the lack of histological diagnosis the epidemiology of DIPG is not completely understood. The aim of this report is to provide population-based data to characterize the descriptive epidemiology of this condition in Canadian children. PATIENTS AND METHODS: A national retrospective study of children and adolescents diagnosed with DIPG between 2000 and 2010 was undertaken. All cases underwent central review to determine clinical and radiological diagnostic characteristics. Crude incidence figures were calculated using age-adjusted (0-17 year) population data from Statistics Canada. Survival analyses were performed using the Kaplan-Meier method. RESULTS: A total of 163 patients with pontine lesions were identified. Central review determined one-hundred and forty-three patients who met clinical, radiological and/or histological criteria for diagnosis. We estimate an incidence rate of 1.9 DIPG/1,000,000 children/year in the Canadian population over a 10 years period. Median age at diagnosis was 6.8 years and 50.3% of patients were female. Most patients presented with cranial nerve palsies (76%) and ataxia (66%). Despite typical clinical and radiological characteristics, histological confirmation reported three lesions to be low-grade gliomas and three were diagnosed as CNS embryonal tumor not otherwise specified (NOS). CONCLUSIONS: Our study highlights the challenges associated with epidemiology studies on DIPG and the importance of central review for incidence rate estimations. It emphasizes that tissue biopsies are required for accurate histological and molecular diagnosis in patients presenting with pontine lesions and reinforces the limitations of radiological and clinical diagnosis in DIPG. Likewise, it underscores the urgent need to increase the availability and accessibility to clinical trials.

Circulating leptin levels are associated with adiposity in survivors of childhood brain tumors.

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.