Development of a Dose-Adjusted Polygenic Risk Model for Anthracycline-Induced Cardiotoxicity.

BACKGROUND: Anthracyclines, which are effective chemotherapeutic agents, cause cardiac dysfunction in up to 57% of patients. The cumulative anthracycline dose is a crucial predictor of cardiotoxicity; however, the cumulative dose alone cannot explain all cardiotoxic events. Strongly associated genetic variants in SLC28A3 , UGT1A6 , and RARG contribute to anthracycline-induced cardiotoxicity in pediatric patients and may help identify those most susceptible. This study aimed to examine how these pharmacogenetic effects are modulated by cumulative anthracycline doses in the development of cardiotoxicity. METHODS: A total of 595 anthracycline-treated children were genotyped and cardiotoxicity cases were identified. A dose-stratified analysis was performed to compare the contributions of SLC28A3 rs7853758, UGT1A6 rs17863783, and RARG rs2229774 variants to the development of cardiotoxicity in low-dose (<150 mg/m 2 cumulative dose) and high-dose (>250 mg/m 2 cumulative dose) patient groups. Logistic regression was used to model the relationships between the cumulative anthracycline dose, genetic variants, and cardiotoxicity in the full cohort. RESULTS: At < 150 mg/m 2 cumulative anthracycline dose, the SLC28A3 protective variant did not reach statistical significance [odds ratio (OR) 0.46 (95% confidence interval (CI) 0.10-1.45), P = 0.23], but it was statistically significant at doses >250 mg/m 2 [OR 0.43 (95% CI 0.22-0.78), P = 0.0093]. Conversely, the UGT1A6 and RARG risk variants were either statistically significant or approaching significance at doses <150 mg/m 2 [OR 7.18 (95% CI 1.78-28.4), P = 0.0045 for UGT1A6 and OR 2.76 (95% CI 0.89-7.63), P = 0.057 for RARG ], but not at doses >250 mg/m 2 [OR 2.91 (95% CI 0.80-11.0), P = 0.10; OR 1.56 (95% CI 0.89-2.75), P = 0.12]. CONCLUSIONS: These findings suggest that the SLC28A3 variant imparts more significant protection for patients receiving higher anthracycline doses, whereas the UGT1A6 and RARG risk variants significantly increased the risk of cardiotoxicity at low anthracycline doses.

Cisplatin-induced nephrotoxicity in childhood cancer: comparison between two countries.

BACKGROUND: Various definitions used to describe cisplatin nephrotoxicity potentially lead to differences in determination of risk factors. This study evaluated incidence of kidney injury according to commonly used and alternative definitions in two cohorts of children who received cisplatin. METHODS: This retrospective cohort study included children from Vancouver, Canada (one center), and Mexico City, Mexico (two centers), treated with cisplatin for a variety of solid tumors. Serum creatinine-based definitions (KDIGO and Pediatric RIFLE (pRIFLE)), electrolyte abnormalities consisted of hypokalemia, hypophosphatemia and hypomagnesemia (based on NCI-CTCAE v5), and an alternative definition (Alt-AKI) were used to describe nephrotoxicity. Incidence with different definitions, definitional overlap, and inter-definition reliability was analyzed. RESULTS: In total, 173 children (100 from Vancouver, 73 from Mexico) were included. In the combined cohort, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity compared to pRIFLE and KDIGO criteria (82.7 vs. 63.6 vs. 44.5%, respectively). Nephrotoxicity and all electrolyte abnormalities were significantly more common in Vancouver cohort than in Mexico City cohort except when using KDIGO definition. The most common electrolyte abnormalities were hypomagnesemia (88.9%, Vancouver) and hypophosphatemia (24.2%, Mexico City). The KDIGO definition provided highest overlap of cases in Vancouver (100%), Mexico (98.6%), and the combined cohort (99.4%). Moderate overall agreement was found among Alt-AKI, KDIGO, and pRIFLE definitions (κ = 0.18, 95% CI 0.1-0.27) in which KDIGO and pRIFLE showed moderate agreement (κ = 0.48, 95% CI 0.36-0.60). CONCLUSIONS: Compared to pRIFLE and KDIGO criteria, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity. pRIFLE is more sensitive to detect not only actual kidney injury but also patients at risk of cisplatin nephrotoxicity, while KDIGO seems more useful to detect clinically significant kidney injury. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.

BACKGROUND: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes. METHODS: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. RESULTS: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]). CONCLUSIONS: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Vertebroplasty as a palliative treatment option for intractable pain in pediatric patients with spinal tumors.

Primary and secondary malignant tumors of the spine are relatively uncommon in the pediatric population but are associated with high morbidity and significantly decreased quality of life due to pain. Local management of these tumors is often challenging due to the importance of maintaining vertebral mechanical integrity as well as the spinal growth potential. Typically, surgery and/or radiation therapy have been used in the primary management of these tumors. However, treatment options become more limited when there is relapse or refractory disease, with re-resection or additional radiotherapy often not being viable therapies. Vertebroplasty is a currently underutilized modality that might provide significant pain palliation in cases of relapsed cancer in the spine.

Vincristine-induced peripheral neurotoxicity: A prospective cohort.

Vincristine-induced peripheral neuropathy (VIPN) is a serious and pervasive problem, affecting 12-78% of pediatric patients, based on retrospective studies. The study objective was to prospectively collect a cohort of well-phenotyped patients receiving vincristine in order to accurately classify and grade their neurotoxicity. All children in British Columbia with leukemia or lymphoma requiring vincristine between 2013 and 2016 were approached for consent. Those recruited were assessed by occupational and physiotherapists at baseline, mid and endpoint of their treatment. Assessments included the Bruininks-Oseretsky Test of Motor Proficiency - 2nd ed. (BOT-2), strength, "Timed up and go" test and vibration sensibility. Seventy-two patients consented (age: 2.0-18.7 years). The majority were below average for age on one or more BOT-2 domains at midpoint (N = 32/45, 71%), which decreased by the endpoint (N = 19/41, 46%, p = .049). Six patients showed severe VIPN throughout treatment (N = 6/53, 11%), defined as a BOT-2 score well below average. Muscle strength for wrist extension/flexion, anterior tibialis and peronei decreased significantly between baseline (Median = 5) and midpoint (Median = 4), with no significant change noted by endpoint. Most patients had normal vibration sensibility in lower (N = 30/60, 50%) and upper limbs (N = 26/38, 68%). In conclusion, with no differences between time points. VIPN is highly prevalent among patients with pediatric cancer, causing significant morbidity and functional deficits. Identification of risk factors would allow for resource appropriation to patients at higher risk, as well as potentially permitting dose escalation in patients with low toxicity to improve survival.

High incidence of acute kidney injury during chemotherapy for childhood acute myeloid leukemia.

BACKGROUND/OBJECTIVES: Childhood acute myeloid leukemia (AML) is a rare and heterogeneous disease. Pediatric data on the epidemiology of acute kidney injury (AKI) in AML are limited. We report on the incidence of AKI in childhood AML and the risk factors associated with AKI episodes. METHODS: A retrospective cohort of 53 patients (≤18 years), with de novo AML, receiving chemotherapy over a 10-year period. All serum creatinine (SCr) levels during therapy-related hospitalizations were assessed to stage AKI episodes as per Kidney Disease: Improving Global Outcomes criteria. Severe AKI was defined as AKI stages 2 or 3 and urine output criteria were not used. AKI risk factors were assessed independently in both cycle 1 alone and combining all chemotherapy cycles. RESULTS: AKI developed in 34 patients (64%) with multiple AKI episodes in 10 patients (46 total episodes). Twenty-four severe AKI episodes occurred in 23 patients (43.4%) with a mean duration of 26.1 days (SD 7.3). In cycle 1, hyperleukocytosis was not predictive of AKI, but severe sepsis was an independent risk factor of severe AKI (odds ratio [OR]: 13.4; 95% CI 1.9-94.9). With cycles combined, all subjects with AKI had severe sepsis and older age (≥10 years) was associated with severe AKI (OR: 20.8; 95% CI 3.8-112.2). CONCLUSION: There was a high incidence of AKI in our AML cohort with a strong association with older age (≥10 years) and severe sepsis. Larger prospective studies are needed to confirm the high burden of AKI and risk factors in this susceptible population.

An initial health economic evaluation of pharmacogenomic testing in patients treated for childhood cancer with anthracyclines.

BACKGROUND: Anthracyclines are a class of highly effective chemotherapeutic drugs commonly used to treat cancer patients. Anthracyclines, however, are associated with the development of serious adverse reactions, including anthracycline-induced cardiotoxicity (ACT). It is not possible, within current practice, to accurately individualize treatment to minimize risk. PROCEDURE: Recently, genetic variants have been associated with the risk of ACT in children. Building on these findings and the related genetic test, a predictive model was developed which classifies pediatric patients by their risk of developing ACT. We assessed the value of this ACT-predictive risk classification in addressing ACT. RESULTS: With current care, the estimated average lifetime cost of ACT is $8,667 per anthracycline-treated patient and approximately 7% of patients are expected to die from ACT. The projected impact of the information from the new predictive model is a 17% reduction in the risk of mortality from ACT and savings of about 6%: lives saved and lower costs. CONCLUSION: The newly identified genetic variants associated with the risk of ACT provide information that allows a more reliable prediction of the risk of ACT for a given patient and can be obtained at a very moderate cost, which is expected to lead to meaningful progress in reducing harm and costs associated with ACT.

Comparison of hypersensitivity rates to intravenous and intramuscular PEG-asparaginase in children with acute lymphoblastic leukemia: A meta-analysis and systematic review.

BACKGROUND: Pegylated-asparaginase (PEG-ASP) is a critical treatment for pediatric acute lymphoblastic leukemia (ALL) and has traditionally been delivered via intramuscular (IM) injection. In an attempt to reduce pain and anxiety, PEG-ASP has increasingly been delivered via intravenous (IV) administration. The study objective was to perform a meta-analysis and systematic review to compare and generate pooled hypersensitivity rates for IM and IV PEG-ASP. METHODS: A systematic literature search was conducted for all epidemiological studies that investigated IV and IM hypersensitivity rates for pediatric ALL. Included studies were critically appraised using the GRACE checklist. Pooled estimates and odds ratios with 95% confidence intervals (CIs) for IM and IV hypersensitivity rates were derived based on either a random or fixed effects model. RESULTS: Four studies satisfied the inclusion criteria and were of adequate quality. The random effects pooled hypersensitivity rates were 23.5% (95% CI 14.7-33.7) and 8.7% (95% CI 5.4-12.8) for IV and IM, respectively. The fixed effects pooled odds ratio after adjusting for publication bias was 2.49 (95% CI 1.62-3.83), indicating a significantly higher risk of hypersensitivity for IV over IM PEG-ASP. This risk is far more pronounced for high-risk (HR) patients compared with standard-risk (SR) patients (IV vs. IM: HR ↑35.2% and SR ↓2.9%). CONCLUSIONS: Although administering PEG-ASP through IV is preferable for patients, it poses a significantly higher risk of hypersensitivity when compared with IM administration, especially for HR patients. We recommend pediatric oncologists consider treating patients with HR pediatric ALL with IM PEG-ASP to reduce the risk of hypersensitivity.

Evolution of a Pediatric Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma on Serial MRI.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare central nervous system tumor, especially in the pediatric population. There are fewer than 20 described cases of pediatric primary central nervous system anaplastic large cell lymphoma. The child described in our case report demonstrated a dramatic evolution of this tumor in the first 4 weeks on serial imaging. METHODS: Serial MRI imaging was performed followed by biopsy and chemotherapy. RESULTS: Initial imaging revealed a T2 hyperintense lesion in the frontal lobe with abnormally enhancing sulci and minimal surrounding edema and diffusion restriction. Serial imaging revealed progressive increase in the degree of gadolinium enhancement, and the hyperintense T2 edema progressed markedly to exert mass effect. The lesion itself grew marginally. Biopsy revealed an anaplastic large cell lymphoma, only described in 14 previous pediatric patient case reports. The patient was successfully treated with chemotherapy and autologous stem cell transplant. CONCLUSIONS: Our case demonstrates the rapidity with which a PCNSL lesion can develop, and the evolution of the imaging characteristics prior to definitive diagnosis and treatment. Serial imaging by MRI may help differentiate the behavior of a PCNSL from other imitating lesions.

Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients.

This guideline provides clinicians with evidence-based recommendations on the use of antifungal prophylaxis in children with cancer and undergoing hematopoietic stem cell transplantation (HSCT). Recommendations are divided into: (1) allogeneic HSCT (2) autologous HSCT (3) acute myeloid leukemia or myelodysplastic syndrome and (4) patients with malignancy and neutropenia for >7 days. A systematic review was conducted and evidence summaries compiled. The quality of evidence and strength of each recommendation was determined using GRADE. Implementation of these recommendations will require adaptation to local context. The contribution of this guideline in the prevention of invasive fungal infections requires prospective evaluation.

Growing teratoma syndrome in intracranial non-germinomatous germ cell tumors (iNGGCTs): a risk for secondary malignant transformation­a report of two cases.

PURPOSE: About 5% of pediatric intracranial germ cell tumors and 20% of non-germinomatous germ cell tumors (NGGCT) progress to growing teratoma syndrome (GTS) following chemoradiotherapy. The growing teratoma is thought to arise from the chemotherapy-resistant, teratomatous portion of a germ cell tumor and is commonly benign but may undergo malignant transformation. METHODS: Two pediatric patients whose intracranial NGGCTs progressed to growing teratomas during chemotherapy and later transformed to secondary malignant tumors after partial resection and radiation therapy (RT). RESULTS: Both tumors were diagnosed by MRI scans and elevated serum and CSF markers. Following normalization of tumor markers with chemotherapy and initial decrease in tumor volume, subsequent imaging showed regrowth during chemotherapy with pathology revealing benign teratoma. RT was administered. Several years following this treatment, further growth was seen with pathology indicating malignant carcinoma in one patient and malignant rhabdomyosarcoma in the other. The patient with carcinoma received palliative care while the patient with the sarcoma received further resection, intensive chemotherapy, and an autologous stem cell transplant and is currently in remission, 36 months since malignant transformation. CONCLUSION: Malignant transformation of presumed residual teratoma has been seldom reported. Treatment of NGGCT involves platinum-based chemotherapy with craniospinal RT and boost to the primary site, with cure rates of around 80%. Teratomas are characteristically chemotherapy and RT resistant and are treated surgically. In the event that residual or growing teratoma is suspected, a complete resection should be considered early in the management as there is a risk of malignant transformation of residual teratoma.

Efficacy of Palivizumab Immunoprophylaxis for Reducing Severe RSV Outcomes in Children with Immunodeficiencies: A Systematic Review.

BACKGROUND: Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care. OBJECTIVE: To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children. METHODS: We searched Ovid MEDLINE and EMBASE for published clinical studies that investigated outcomes of palivizumab use in children. We included clinical trials, cohort studies, and case-control studies. The primary outcomes were RSV-related or respiratory viral infection-related hospitalizations, or RSV-related mortality. This systematic review was registered in PROSPERO (ID CRD42021248619) and is reported in accordance with the PRISMA guidelines. RESULTS: From the 1993 records, six studies were eligible and included, for a total of 625 immunocompromised children with an heterogeneous composition of primary and acquired immunodeficiencies enrolled from palivizumab programs. There were no intervention studies. None of the studies included a control group. RSV hospitalizations were infrequent (0%-3.1% of children). Most children included received palivizumab, although one study (n = 56) did not specify how many received palivizumab. RSV mortality was neither observed, in three studies, nor reported, in three other studies. CONCLUSIONS: The evidence supporting the use of palivizumab for prevention of severe RSV disease in immunocompromised children remains extremely limited and appears insufficient to justify prioritizing this intervention as the current standard of care over alternative interventions.

Outcome of infants and young children with newly diagnosed ependymoma treated on the "Head Start" III prospective clinical trial.

This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma treated on the prospective multinational "Head Start" III clinical trial. Between April 2004 and July 2009, 19 children with newly-diagnosed ependymoma were enrolled. All children were to receive five induction chemotherapy cycles followed by one consolidation cycle of myelo-ablative chemotherapy and autologous hematopoietic cell rescue. Children between 6 and 10 years of age or with residual tumor prior to consolidation were to receive irradiation thereafter. Median age of 19 children (8 female) was 20 months at diagnosis. Median follow up was 44 months. The primary site was infratentorial in 11 and supratentorial in 8 patients. Gross total resection was achieved in 10 patients. After induction chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response (CR), while only one of six infratentorial patients with residual disease achieved CR. Three infratentorial patients developed progressive disease during induction chemotherapy. All four infratentorial patients with residual disease who underwent autologous hematopoietic cell transplant, failed to achieve CR. Four patients received focal irradiation following chemotherapy. The 3-year event free survival (EFS) and overall survival (OS) for supratentorial ependymoma were 86 ± 13 % and 100 % respectively. The 3-year EFS and OS for infratentorial ependymoma were 27 ± 13 % and 73 ± 13 % respectively. The role of intensive induction and consolidation chemotherapy in deferring irradiation should be investigated further in children with supratentorial ependymoma with residual disease following surgery. This approach appears ineffective in children with infratentorial ependymoma in the absence of irradiation.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Nephrotic syndrome developing during induction chemotherapy for childhood acute lymphoblastic leukemia.

This report is the first to document minimal change nephrotic syndrome occurring during induction chemotherapy for childhood acute lymphoblastic leukemia (ALL). This occurrence lends further support to the theory of immune cell dysregulation being central to the pathogenesis of nephrotic syndrome in ALL, rather than alternative postulations that this association is due to an increased risk of malignancy secondary to prior immunosuppressive treatment for nephrotic syndrome.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

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.

Childhood, adolescent, and young adult cancer survivors research program of British Columbia: objectives, study design, and cohort characteristics.

BACKGROUND: The Childhood, Adolescent, and Young Adult Cancer Survivors Research Program (CAYACS) has been established in the province of British Columbia (BC), Canada, to carry out research into late effects and survivor care in multiple domains, and to inform policy and practice. PROCEDURE: This program identifies a survivor cohort and comparison groups from population-based registries and links their records to population-based files of outcomes and outcome determinants, to create a research database and conduct studies of long-term outcomes and care. RESULTS: The initial cohort consisted of all 5-year survivors of cancer or a tumor diagnosed under age 25 years from 1970 to 1995, who were residents in BC at the time of diagnosis, and followed till 2000 (3,841 subjects). Seven percent have died, and 77% have treatment information available. Data on death and second cancer occurring in BC are available. Late morbidity and healthcare utilization information is available for 68% of survivors (79% of those diagnosed from 1981). Education outcomes are available for 71% of those born during 1978-1995 and diagnosed under age 15 years. CONCLUSIONS: Use of registries, administrative databases, and record linkage methodologies is a cost-effective and comprehensive means to conduct survivorship research. This program should add to knowledge of risks of late effects and impacts on care, inform development of strategies to manage risks, evaluate the effects of surveillance and interventions, and assess new risks as the cohort ages, more recent survivors enter the cohort, and treatments change.