Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

Epidemiology of clinically unsuspected venous thromboembolism in children with cancer: A population-based study from Maritimes, Canada.

Inconsistencies in the definition of clinically unsuspected venous thromboembolism (VTE) in pediatric patients recently led to the recommendation of standardizing this terminology. Clinically unsuspected VTE (cuVTE) is defined as the presence of VTE on diagnostic imaging performed for indications unrelated to VTE in a patient without symptoms or clinical history of VTE. The prevalence of cuVTE in pediatric cancer patients is unclear. Therefore, the main objective of our study was to determine the prevalence of cuVTE in pediatric cancer patients. All patients 0-18 years old, treated at the IWK in Halifax, Nova Scotia, from August 2005 through December 2019 with a known cancer diagnosis and at least one imaging study were eligible (n = 743). All radiology reports available for these patients were reviewed (n = 18,120). The VTE event was labeled a priori as cuVTE event for radiology reports that included descriptive texts indicating a diagnosis of thrombosis including thrombus, central venous catheter-related, thrombosed aneurysm, tumor thrombosis, non-occlusive thrombus, intraluminal filling defect, or small fragment clot for patients without documentation of clinical history and or signs of VTE. A total of 18,120 radiology reports were included in the review. The prevalence of cuVTE was 5.5% (41/743). Echocardiography and computed tomography had the highest rate of cuVTE detection, and the most common terminologies used to diagnose cuVTE were thrombus and non-occlusive thrombus. The diagnosis of cuVTE was not associated with age, sex, and type of cancer. Future efforts should focus on streamlining radiology reports to characterize thrombi. The clinical significance of these cuVTE findings and their application to management, post-thrombotic syndrome, and survival compared to cases with symptomatic VTE and patients without VTE should be further studied.

Bacterial heat shock protein genes during induction chemotherapy in pediatric patients with acute lymphoblastic leukemia.

Background: Heat shock proteins (HSP) protect cancer cells. Gastrointestinal bacteria contain HSP genes and can release extracellular vesicles which act as biological shuttles. Stress from treatment may result in a microbial community with more HSP genes, which could contribute to circulating HSP levels. Methods: The authors examined the abundance of five bacterial HSP genes pre-treatment and during induction in stool sequences from 30 pediatric acute lymphoblastic leukemia patients. Results: Decreased mean HTPG counts (p = 0.0024) pre-treatment versus induction were observed. During induction, HTPG, Shannon diversity and Bacteroidetes decreased (p = 7.5e-4; 1.1e-3; 8.6e-4), while DNAK and Firmicutes increased (p = 6.9e-3; 9.2e-4). Conclusion: Understanding microbial HSP gene community changes with treatment is the first step in determining if bacterial HSPs are important to the tumor microenvironment and leukemia treatment.

Survival effect of complete surgical resection of the primary tumor in patients with metastatic, high-risk neuroblastoma in a large Canadian cohort.

PURPOSE: To determine whether extent of surgical resection of the primary tumor correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma. METHODS: Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001 and 2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumor based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem cell transplant (SCT). RESULTS: One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete versus incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p = .008 and p = .002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT, and surgical resection, only complete resection was associated with statistically significant improved 3 year EFS and OS, HR = 0.48 (0.29-0.81; p = .006) and HR = 0.42 (0.24-0.73; p = .002). CONCLUSIONS: In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival.

Asparaginase activity monitoring and management of asparaginase hypersensitivity reactions in Canada.

INTRODUCTION: Pegaspargase can cause anti-asparaginase antibody formation, which can decrease its effectiveness without causing any clinically apparent reaction (silent inactivation). When a patient has silent inactivation, a switch to Erwinia anti-asparaginase is warranted, but there is currently a global shortage of Erwinia. The only way to identify silent inactivation is to measure an asparaginase level. However, routine asparaginase level monitoring is not currently standard of care at all Canadian centers. This study aims to identify variations in practice regarding asparaginase level monitoring and Erwinia use. METHODS: A 21-item survey was developed using OPINIO software and distributed to all Pediatric Hematology-Oncologists in Canada from February to October 2020. RESULTS: Respondents represented 15 hospitals across each region of Canada (response rate = 52%). Only 39.2% of respondents reported routinely measuring asparaginase levels, yet 53% of respondents have modified therapy from pegaspargase to Erwinia in up to half of their patients. The most common reason for not measuring asparaginase levels was not knowing how to use levels clinically (25.5%). There was variation in the timing of levels and their target. CONCLUSIONS: We identified substantial variation in asparaginase activity monitoring practices across Canada. Therefore, future research should aim to develop a national practice guideline on asparaginase activity monitoring.

Postdischarge Iron Status in Very Preterm Infants Receiving Prophylactic Iron Supplementation after Birth.

OBJECTIVE: To determine postdischarge iron status and associated factors in very preterm infants. STUDY DESIGN: A retrospective cohort study was conducted through a provincial database on all very preterm infants born in Nova Scotia between 2005 and 2018. As a standard of care, all infants received prophylactic iron supplements starting at 2-4 weeks of chronological age and were tested for iron deficiency at 4 or 6 months corrected age. Iron deficiency was defined as serum ferritin <20 g/L at 4 months or <12 g/L at 6 months. Multivariate logistic regression analysis identified factors associated with iron deficiency. RESULTS: Among 411 infants, 132 (32.1%) had iron deficiency and 11 (2.7%) had iron deficiency anemia. The prevalence of iron deficiency decreased over time, from 37.6% in 2005-2011 to 25.8% in 2012-2018. Gestational hypertension in the mother (P = .01) and gestational age <27 weeks (P = .02) were independent risk factors for iron deficiency. In addition, the odds of iron deficiency were lower in the mixed-fed group (ie, with breast milk and formula combined) compared with the exclusive formula-fed group (P = .01). CONCLUSIONS: Iron deficiency was prevalent in 32% of the very preterm infants despite early iron prophylaxis. These results demonstrate the importance of monitoring iron stores during preterm follow-up. Information about risk factors is important to mitigate iron deficiency in very preterm infants.

Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: A report from CYP-C.

There are conflicting data about whether the development of cancer-associated thrombo-embolism (TE) negatively impacts survival in children. The objective was to determine whether TE during treatment was associated with overall survival (OS) and event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL). We performed a population-based retrospective cohort study using the Cancer in Young People-Canada registry. Children <15 years of age were diagnosed with de novo ALL (2000-2016). The primary exposure variable was radiologically-confirmed thrombo-embolism requiring medical intervention. Multivariable Cox regression models were used to determine the impact of thrombo-embolism on survival, where TE was time-dependent. We included 2006 children (median age: 4 years, 88.5% precursor B-cell ALL). Thrombo-embolism occurred in 113 patients (5.6%), at a median time of 107 days (interquartile range: 35-184 days) after ALL diagnosis. Among standard/low-risk patients, 41/1165 (3.5%) developed TE while among high/very high-risk patients, 72/841 (8.6%) developed TE. Patients with TE had a significantly worse OS (adjusted HR [aHR] of death: 2.61, 95% CI: 1.62-4.22, p < 0.001) and EFS (aHR of an event [death, relapse, second malignancy]: 2.03, 95% CI: 1.35-3.05, p = 0.001), compared with patients without TE. No statistically significant difference was seen in standard/low risk ALL for OS and EFS, but TE was associated with a significantly lower OS and EFS in children with high/very high-risk ALL (aHR of death: 2.90, 95% CI: 1.79-4.72, p < 0.001; aHR of an event: 2.02, 95% CI: 1.30-3.12, p = 0.002). Thus, TE led to a statistically significant reduction in OS and EFS in children with high risk/very high-risk leukemia.

Optimizing pharmacologic thromboprophylaxis use in pediatric orthopedic surgical patients through implementation of a perioperative venous thromboembolism risk screening tool.

BACKGROUND: Although rare, venous thromboembolic events (VTE) are a significant challenge in pediatric orthopedic surgical patients (POSP). A VTE thromboprophylaxis screening tool was developed and implemented in POSPs at the IWK Health Centre since October 2016. OBJECTIVES: This retrospective cohort study was designed to evaluate and assess the impact of the VTE thromboprophylaxis screening tool in terms of use of thromboprophylaxis in POSP. METHODS: Using the tool, POSPs were screened and were categorized into risk groups. Patient groups were compared and spearman correlation analysis was performed to show the strength of association between risk factors and thromboprophylaxis. Retrospective screening of pre-algorithm patients who received thromboprophylaxis was done to further assess the screening tool. RESULTS: After the implementation of the VTE thromboprophylaxis screening tool in POSPs, there was a 47.9% reduction in the use of thromboprophylaxis (P = 0.046) as compared with before. Neither VTE nor significant bleeding complications occurred before or after screening tool implementation. Compliance with the screening tool was excellent (100% of patients in the high-risk category received thromboprophylaxis). High-risk patients were more likely to have body mass index  > 30 (35.7%), limited/altered mobility (57.1%), and to be undergoing a complicated/repeat surgery (64.3%). CONCLUSIONS: The present study demonstrates successful implementation of a VTE thromboprophylaxis screening tool that resulted in significant reduction in use of thromboprophylaxis in POSPs with no increase in VTE or change in bleeding complications.

The impact of the host intestinal microbiome on carcinogenesis and the response to chemotherapy.

The microbiome consists of all microbes present on and within the human body. An unbalanced, or 'dysbiotic' intestinal microbiome is associated with inflammatory bowel disease, diabetes and some cancer types. Drug treatment can alter the intestinal microbiome composition. Additionally, some chemotherapeutics interact with microbiome components, leading to changes in drug safety and/or efficacy. The intestinal microbiome is a modifiable target, using strategies such as antibiotic treatment, fecal microbial transplantation or probiotic administration. Understanding the impact of the microbiome on the safety and efficacy of cancer treatment may result in improved treatment outcome. The present review seeks to summarize relevant research and look to the future of cancer treatment, where the intestinal microbiome is recognized as an actionable treatment target.

Lay abstract The microbiome describes all of the microorganisms (including bacteria, viruses and fungi) that are normally present on and inside the human body. Some diseases, including cancer, can be caused or worsened by an 'unbalanced' or 'unhealthy' gut microbiome. Some drugs that are given to people who have cancer can change the microbiome. Importantly, components of the gut microbiome can also change how a cancer drug will work in someone. We can change the microbiome in certain ways, like by giving someone antibiotics. Understanding how the microbiome influences the way anticancer drugs work is important because it could help us understand how to make cancer treatment safer and more effective. This review article summarizes available research on the impact of the microbiome on cancer treatment.

Pediatric CNS Tumor Patients Have Significantly Lower Requirement of Tissue Plasminogen Activator for Episodes of Central Venous Catheter Dysfunction Compared With Other Pediatric Oncology Patients: Results of a Population-based Cohort Study.

PURPOSE: Central venous catheters (CVCs) are an important component of care delivery in pediatric oncology patients. However, CVC dysfunction is a common problem. Tissue plasminogen activator (tPA) is often administered to re-establish function, however, specific experience in pediatric patients with central nervous system (CNS) tumors is lacking. The goal of this study was to investigate the CVC experience and use of tPA for episodes of CVC dysfunction in pediatric patients with CNS tumors in comparison with other patients. METHODS: Medical records of all pediatric oncology patients from the 4 Atlantic provinces in Canada (Nova Scotia, New Brunswick, Prince Edward Island, and Newfoundland and Labrador) were reviewed. Data collected included demographics, treatment, details of CVCs along with CVC dysfunction, and tPA use. RESULTS: The cohort consisted of 1152 pediatric oncology patients, 222 (19.3%) of whom had CNS tumors. CVC dysfunction requiring tPA administration occurred in 12 (5.4%) of patients with CNS tumors compared with 182 (19.6%) of patients with non-CNS tumors (P=0.0001). Multivariate logistic regression analysis showed that administration of tPA for CVC dysfunction was 2.5 times more likely in patients with non-CNS tumors than those with CNS tumors (P=0.012; 95% confidence interval, 1.3-4.9). CONCLUSIONS: Our study showed that pediatric patients with CNS tumors require significantly less frequent administration of tPA for episodes of CVC dysfunction than patients with non-CNS tumors after adjusting for confounding factors. Hypotheses for this include: potential biologic differences of tumors, the role of the blood-brain barrier, or systematic differences in intensity of treatments.

Use of Tissue Plasminogen Activator as a Surrogate Measure for Central Venous Catheter Dysfunction and Survival Outcome in Children with Cancer: A Population-Based Retrospective Cohort Study.

Central venous catheter (CVC) dysfunction is often associated with thrombosis, which in turn has been linked with poorer survival outcomes in cancer patients. Our objective was to examine the association of tissue plasminogen activator (tPA) administration as a surrogate measure of CVC dysfunction with survival in pediatric cancer patients. The present study uses data from a population-based retrospective cohort of pediatric oncology patients from the Canadian Maritime provinces treated between 2000 and 2017 at the IWK Health Centre, Halifax, NS. Demographics, diagnosis, date of death or date of last visit, and tPA use for CVC dysfunction were obtained from clinical databases and the provincial Cancer in Young People in Canada registry. The association between tPA administration and survival was examined using a Cox regression model adjusted for sex, age at diagnosis, cancer type, thrombosis, CVC duration, diagnosis era, and treatment modalities. Out of 821 patients, 206 received one or more doses of tPA during upfront therapy. The death rate was 21% and 15% respectively in patients who did and did not receive tPA. In the adjusted regression model, after receiving one or more doses of tPA, children had significantly poorer survival as compared to those that did not receive tPA (HR: 1.496, 95% CI: 1.019, 2.197). CVC dysfunction may be associated with a poorer prognosis in pediatric cancer patients. Future studies should corroborate these findings in other populations, examine the influence of other potential confounders, and determine the role of CVC dysfunction in prognostic models of cancer survival.

Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients.

Venous thromboembolism (VTE) has been recognized as a rare but potentially serious complication in pediatric orthopedic patients. However, standardized guidelines for screening and management of at-risk patients do not exist. The aim of the study was to develop a VTE prophylaxis screening tool for postoperative orthopedic patients after conducting an institutional needs assessment survey. A needs assessment survey was conducted after institutional ethics board approval. Development of perioperative VTE prophylaxis algorithm for pediatric orthopedic surgical patients was planned after thorough literature review, consultation with national and international experts as well as using a modified nominal and consensus development conference (serial meetings) method for reaching a consensus. NAS as well as discussion with stakeholders indicated support for development of perioperative VTE prophylaxis algorithm for orthopedic patients. Using above methods, a VTE prophylaxis algorithm was developed and implemented at IWK Health Center. The present study involved development of a perioperative VTE prophylaxis algorithm for pediatric orthopedic surgical patients that could be easily and rapidly administered as a point of care assessment tool.

Enrollment on clinical trials does not improve survival for children with acute myeloid leukemia: A population-based study.

BACKGROUND: It is questionable whether enrollment on clinical trials offers any survival advantage at the population level over standard-of-care treatment. The objectives of this study were to describe the impact of trial enrollment on event-free survival and overall survival in pediatric acute myeloid leukemia (AML) using the Cancer in Young People in Canada (CYP-C) database. METHODS: Children were included if they had had AML newly diagnosed between ages birth and 14 years from 2001 to 2012. CYP-C is a national pediatric cancer population-based database that includes all cases of pediatric cancer diagnosed and treated at 1 of the 17 tertiary pediatric oncology centers in Canada. Univariate and Cox proportional hazards models were used to evaluate the impact of initial trial enrollment on survival. RESULTS: In total, 397 eligible children with AML were included in the analysis, of whom 94 (23.7%) were enrolled on a clinical trial at initial diagnosis. The most common reason for non-enrollment was that no trial was available. The event-free survival rate at 5 years was 57.8% ± 5.2% for those enrolled versus 54.8% ± 2.9% for those not enrolled (P = .75). The overall survival rate at 5 years was 70.1% ± 4.9% for those enrolled versus 66.3% ± 2.8% for those not enrolled (P = .58). Enrollment on a trial was not associated with improved event-free or overall survival in multiple regression analyses. CONCLUSIONS: Enrollment on a clinical trial was not associated with improved survival for children with AML in a population-based cohort. Rationale for trial enrollment should not include the likelihood of benefit compared with non-enrollment.

Enrolling children with acute lymphoblastic leukaemia on a clinical trial improves event-free survival: a population-based study.

BACKGROUND: The objectives of this study were to describe the impact of trial enrollment at diagnosis on event-free and overall survival in paediatric acute lymphoblastic leukaemic (ALL) using a population-based approach. METHODS: We conducted a retrospective cohort study that included children newly diagnosed with ALL between 1 and 14 years of age. The data source was the Cancer in Young People in Canada (CYP-C) national paediatric cancer population-based database. We conducted univariate and multiple Cox proportional hazards models. RESULTS: There were 2569 children with ALL; 1408 (54.8%) were enrolled on a clinical trial at initial diagnosis. Event-free survival at 5 years was 89.8%±0.9 vs 84.1%±1.2. (P<0.0001) for those enrolled and not enrolled on a clinical trial, respectively. Overall survival at 5 years was higher for those enrolled (94.1%±0.7) vs not enrolled (90.5%±1.0; P=0.001). In a model that adjusted for demographic, leukaemic and socioeconomic factors, enrollment on trials was significantly associated with better event-free survival (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.47-0.95; P=0.023), but not overall survival (HR 0.69, 95% CI 0.44-1.08; P=0.102). CONCLUSIONS: Event-free survival was significantly better in children with ALL enrolled on a clinical trial. Future research should identify barriers to clinical trial enrollment for children with ALL.

Correction to: The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study.

The Figure 1 used in the originally published version of this article was incorrect.

The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study.

Venous thromboembolism (VTE) is a well-recognized complication in pediatric oncology patients. Studies in adult oncology patients have suggested a potential negative association between VTE and survival, but this association has not been examined in pediatric patients yet. The aim of this study was to assess the association of VTE with survival in pediatric oncology patients. Data from all pediatric oncology patients treated at the two tertiary care centers in Atlantic Canada were pooled to create a population-based cohort. The association between VTE and survival was analyzed using a Cox proportional hazards model stratified by diagnosis group (leukemia, lymphoma, and other; sarcoma) and adjusted for age at diagnosis and sex. Out of 939 patients included in this study, 73 had a VTE (8%) and 131 (14%) patients died during the study period. Children in the leukemia/lymphoma/other group with a VTE had significantly poorer survival relative to children in the same group who did not have a VTE. Although children with sarcoma and VTE had poorer survival compared to children with sarcoma with no VTE, this association was not statistically significant. In this population-based study, we found a negative association between VTE and survival in pediatric oncology patients. If future studies confirm this association, this finding may have prognostic implications and potentially offer new avenues for the management of pediatric patients with cancer.

Need for tissue plasminogen activator for central venous catheter dysfunction is significantly associated with thrombosis in pediatric cancer patients.

BACKGROUND: Central venous catheter (CVC) dysfunction is a common complication among pediatric cancer patients. Tissue plasminogen activator (tPA) is administered to resolve CVC dysfunction. The present study was designed to determine risk factors associated with requirement of tPA for CVC dysfunction and to assess the clinical impact of CVC dysfunction in terms of CVC loss and venous thrombotic events (VTE). PROCEDURE: Case records of all pediatric patients with cancer from the Maritimes, Canada were reviewed following ethics approval. Data regarding demographics, clinical diagnosis, CVC dysfunction, characteristics of CVCs, and VTE were pooled from multiple data sources. RESULTS: Seven hundred and forty-one patients required ≥1 CVC. 26.3% of patients required tPA for ≥1 episodes of CVC dysfunction. Requirement of one or more doses of tPA for episodes of CVC dysfunction increased the odds of VTE by two times (95% confidence interval, 1.1-3.6). Patients that required ≥1 doses of tPA required significantly more CVCs (2.05 ± 1.29 per individual patient, 55% of the patients needed >1 CVCs) as compared to the remainder (1.52 ± 0.95 per individual patient, 32% needed >1 CVCs) (P = 0.0001). Multivariate analysis revealed age > 10 years, diagnosis of sarcoma, and tunneled line were independently associated with tPA requirement. CONCLUSION: We determined independent risk factors associated with requirement of tPA for CVC dysfunction. Requirement of tPA for CVC dysfunction was associated with significantly increased risk of VTE and requirement of more CVCs. These observations can assist in identification of patients at increased risk of CVC dysfunction and inform approaches to reduce CVC loss and VTE.

Peripherally Inserted Central Catheters in Pediatric Oncology Patients: A 15-Year Population-based Review From Maritimes, Canada.

The present population-based study evaluates the management and complications of peripherally inserted central catheters (PICC) in all pediatric oncology patients diagnosed in Maritimes, Canada from 2000 to 2014. A total of 107 PICCs were placed in 87 (10.1%) pediatric oncology patients. A high percentage (33% and 44%, respectively) of the first and second PICC lines was associated with complications. Thrombosis, occlusion, and infection were the most frequent complications. Age above 10 years and left body side of insertion were significantly associated with PICC complications. Given the frequent use of PICCs and the high incidence (>33%) of complications, there is a need to mitigate PICC line complications.

Most children with cancer are not enrolled on a clinical trial in Canada: a population-based study.

BACKGROUND: Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and factors associated with enrollment on trials. METHODS: In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012. We used data from the Cancer in Young People in Canada (CYP-C) national pediatric cancer population-based database. CYP-C captures all cases of pediatric cancer (0-14 years) diagnosed and treated at one of the 17 tertiary pediatric oncology centers in Canada. Non-enrollment was evaluated using univariate and multiple logistic regression analysis. RESULTS: There were 9204 children with cancer included, of whom 2533 (27.5%) were enrolled on a clinical trial. The most common reasons cited for non-enrollment were lack of an available trial (52.2%) and physician choice (11.2%). In multiple regression, Asian and Arab/west Asian race were associated with lower enrollment (P = 0.006 and P = 0.032 respectively). All cancer diagnoses were more likely to be enrolled compared to astrocytoma and children with acute lymphoblastic leukemia had an almost 18-fold increased odds of enrollment compared to astrocytoma (P < 0.0001). Greater distance from the tertiary care center was independently associated with non-enrollment (P < 0.0001). CONCLUSIONS: In Canada, 27.5% of children with cancer are enrolled onto therapeutic clinical trials and lack of an available trial is the most common reason contributing to non-enrollment. Future research should better understand reasons for lack of trial availability and physician preferences to not offer trials.

Incidence and characteristics of venous thrombotic events in pediatric cancer patients: A 20-year experience in the Maritimes, Canada.

OBJECTIVE: Venous thrombotic events (VTE) are a well-recognized complication in pediatric cancer patients. Population-based data on the incidence and characteristics of VTE in all pediatric cancer patients are limited. This information is crucial to identify patients at high risk and design targeted interventions accordingly. The present study was designed to determine the incidence and characteristics of VTE in the pediatric oncology population. PARTICIPANTS: We conducted a retrospective, population-based, cohort study of patients treated in the Maritimes, Canada between 1995 and 2015. RESULTS: There were 1210 pediatric hematology/oncology patients from the Maritimes, Canada, treated at the IWK Health Centre between 1995 and 2015. Fifty-eight (4.8%) experienced at least 1 VTE and the majority of patients experienced it within 6 months of cancer diagnosis. The median age of patients who experienced VTE was 10.7 years (SD = 6.0). The most common presenting symptom of thrombosis was central venous line dysfunction, and the most common location for thrombosis was within the upper venous system. We observed that 65.6% of the patients with VTE required >1 central venous catheters (CVC). The presence of a VTE increased the odds of requiring >1 CVC to 3.6 (95% confidence interval: 1.76-7.3). CONCLUSION: Thus, in this large, population-based study, we present the incidence and characteristics of VTE in the pediatric oncology population and demonstrate the clinical impact of VTE in terms of loss of CVC. Larger, prospective studies are required to confirm these findings and to develop a risk model for managing and preventing VTE in this patient population.