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Background: The treatment of BRAF V600E gliomas with BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been increasingly integrated into clinical practice for pediatric low-grade gliomas (PLGGs) and pediatric high-grade gliomas (HGGs). However, some questions remain unanswered, such as the best time to start targeted therapy, duration of treatment, and discontinuation of therapy. Given that no clinical trial has been able to address these critical questions, we developed a Canadian Consensus statement for the treatment of BRAF V600E mutated pediatric as well as adolescent and young adult (AYA) gliomas. Methods: Canadian neuro-oncologists were invited to participate in the development of this consensus. The consensus was discussed during monthly web-based national meetings, and the algorithms were revised until a consensus was achieved. Results: A total of 26 participants were involved in the development of the algorithms. Two treatment algorithms are proposed, one for the initiation of treatment and one for the discontinuation of treatment. We suggest that most patients with BRAF V600E gliomas should be treated with BRAFis ± MEKis upfront. Discontinuation of treatment can be considered in certain circumstances, and we suggest a slow wean. Conclusions: Based on expert consensus in Canada, we developed algorithms for treatment initiation of children and AYA with BRAF V600E gliomas as well as a discontinuation algorithm. [ABSTRACT FROM AUTHOR]

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children. [ABSTRACT FROM AUTHOR]

[12] Requiring GMP certification for medical cannabis products could, however, result in a 2-tier regulatory system (with GPP and GMP certification required for recreational and medical cannabis products, respectively), and some producers may elect to exit the medical cannabis market. Health Canada also maintains a system for reporting adverse events associated with cannabis products on its Canada Vigilance website.[9] Licensed cannabis producers are required to report serious adverse events associated with the use of their products, but it is not mandatory for health care providers to do so. Children with chronic debilitating illness and pain are increasingly using cannabis for medical purposes, particularly when conventional treatment options have limited benefit or substantial adverse effects. [Extracted from the article]

Background: Tumors of the spinal cord are exceedingly rare in infancy and only a paucity of literature exists describing the spectrum of this disease and its management. The objectives of our study were to describe the demographic characteristics of spinal cord tumors (SCT) in children less than 3 years of age at diagnosis and to review their treatment and outcome. Methods: A national retrospective chart review was conducted on patients under the age of 3 years diagnosed with a primary tumor of the central nervous system (CNS) between 1990 and 2005 across Canada. Inclusion criteria were: age ≤3 years, histologic confirmation of the diagnosis, and residency in Canada. A centralized database was created and information regarding SCT was extracted. Results: Twenty-five of five hundred seventy-nine patients (4.3%) in the data bank had a SCT. The majority of tumors were low-grade astrocytomas (14/25). Leptomeningeal dissemination based on neuroradiologic imaging and/or cerebrospinal fluid cytology was present in five (20%) patients. The majority of patients underwent an incomplete surgical resection (52%). Most patients (64%) did not receive postoperative radiotherapy or chemotherapy. Seventy-two percent (18/25) developed recurrent/progression of disease. Overall 2- and 5-year survival for low- and high-grade malignancies was 93 ± 6.4% and 37.5 ± 17.1% respectively. Significant predictors of survival included mean duration of symptoms prior to initial diagnosis and recurrence/progression of disease. Conclusions: Relapse/progression of disease in infant SCT is frequent. Prolonged survival of low-grade tumors is possible with further therapy; however, the prognosis of high-grade malignancies remains poor. [ABSTRACT FROM AUTHOR]

Background: Choroid plexus tumors (CPT) are rare pediatric tumors. A population-based study on choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP) was carried out to describe the incidence, demographic, and outcome data and to identify potential prognostic factors. Methods: The CPT population from the Canadian databank of CNS tumor in children ≤36 months diagnosed between 1990 and 2005 was reviewed Results: Out of the 579 reported cases of CNS tumors, 37 were CPT. The annual age-adjusted incidence rate was 0.22 + 0.12 (95% CI 0.16-0.28)/100,000 children <3 years. There were 21 (56.7%) CPP and 16 (43.3.5%) CPC. Twenty patients (54%) were males. Median age at diagnosis was 7 months(range 0-30). Ten patients(62.5%) with CPC and one with CPP were metastatic at diagnosis. Twenty patients with CPP (95%) had a complete resection, whereas 6/16 CPC (37.5%) achieved a resection >90%. Fourteen CPC patients received adjuvant chemotherapy. None of the 37 patients received adjuvant radiation. At completion of survey, all CPP and five CPC were alive. Median survival time for CPC patients was 15 months (0-120). One death was related to intraoperative hemorrhage, another to chemotherapy-induced toxicity, and one to secondary AML. Age at diagnosis, degree of resection and metastatic status were not significant prognostic factors for CPC. Conclusion: By contrast to CPC, CPP have an excellent prognosis following surgery alone. Survival of CPC remains poor. However, these data may suggest adjuvant chemotherapy can alter the aggressive natural history of CPC. As with other rare CNS tumors, international collaboration is required to identify optimal therapy. [ABSTRACT FROM AUTHOR]

While it is recognized that research priorities should reflect and integrate the perspectives and needs of patients along with those of health professionals and researchers, it remains challenging to actualize such priorities into tangible research projects. Targeted dissemination is required to catalyze research on these priorities. To create awareness of and inspire action toward actualizing the top 10 retinoblastoma research priorities in Canada, Canadian Retinoblastoma Research Advisory Board (CRRAB) members developed a wide range of dissemination tools and processes. These resources, co-produced with patients, were instrumental to CRRAB sharing the top 10 priorities internationally to mobilize action toward solving them., (Copyright © 2022 Longwoods Publishing.)

Background: The use of cannabis for medical purposes by pediatric patients is expanding across Canada; however, supporting evidence, federal regulations and treatment guidelines are lacking. To understand factors affecting treatment decisions in this landscape, we sought to delineate clinician perspectives, ethics priorities and values for cannabis authorization., Methods: We sampled participants purposefully through Canadian Childhood Cannabinoid Clinical Trials listservs, which include the majority of pediatric oncologists and palliative care physicians practising in Canada, among many other pediatric physicians and clinicians. Inclusion criteria were being a practising clinician in Canada, involvement in the care of children and willingness to be interviewed regardless of stance on medical cannabis. In November and December 2020, we conducted semistructured interviews focusing on principles, values and priorities, including medical, professional, regulatory, evidentiary and social considerations, for authorizing medical cannabis to children. Interviews were recorded, transcribed and analyzed by means of deductive and inductive thematic methods., Results: We conducted 18 interviews with a diverse group of clinicians representing a range of specialties within pediatric care, including neurology, palliative care, oncology, family medicine and pharmacology. The interviews yielded 4 themes and 12 subthemes related to a priori (medical, professional, regulatory, evidentiary and social themes) and emergent themes. The 4 themes of access, relationships and relational autonomy (autonomy within relationships), medically appropriate use and research priorities were grounded in principles of harm reduction. Participants described problematic authorization procedures that negatively affect patient use. Principles associated with relational autonomy were highlighted as a feature of open clinical communication. Benefits of appropriate medical uses weighed positively over risks, even in the context of potential effects on neurodevelopment. Participants expressed that more research is essential to align medical cannabis with biomedical standards., Interpretation: Clinicians reported pursuing ethical use of medical cannabis for pediatric patients and prioritizing their safety under principles of harm reduction. There is a need for evidence about neurodevelopmental risks, support for research, treatment guidelines and greater knowledge about stakeholder perspectives to alleviate burdens related to use of medical cannabis for pediatric patients in Canada., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Competing Interests: Competing interests: Richard Huntsman and Lauren Kelly are co-chairs of the Health Canada scientific advisory committee on health products containing cannabis, whose opinion is not reflected or guaranteed within. Lauren Kelly holds a Mitacs Accelerate award in partnership with Canopy Growth, unrelated to this manuscript. Juan Pablo Appendino reports honoraria from Pendopharm, Sunovion and UCB, as well as board or committee membership with the Canadian League Against Epilepsy, the Canadian Society of Clinical Neurophysiologists, the Canadian Neurological Sciences Federation and the Iberoamerican Academy of Pediatric Neurology. Richard Bélanger is on the cannabis committee of the Canadian Paediatric Society. Bruce Crooks reports participation on the data safety monitoring board of the ReRAD study, as well as membership with the Nova Scotia chapter advisory board and medical advisory committee of Make a Wish Foundation Canada. Evan Lewis has an unpaid position as medical advisor to the JMCC Canada Corp., and also reports honoraria from Spectrum Therapeutics. Alexander Repetski has an unpaid advisory position with Strainprint. Michael Rieder is a member of the drug safety monitoring board for a study exploring the use of medical cannabis for headache in children and is the principal author of the Canadian Paediatric Society’s statement on medical cannabis for children. Regis Vaillancourt reports consulting fees from Harvest Medicine. No funding was received to author this manuscript. No other competing interests were declared.

Background: Venous thromboembolism (VTE) is a well-recognized complication in pediatric cancer patients. It has been demonstrated that the incidence of VTE in pediatric patients with central nervous system (CNS) tumors is lower than that of patients with other cancers. Risk factors for developing cancer-related thrombosis are numerous and can include patient, disease, or treatment-related influences. The present study was designed to assess the VTE incidence in a pediatric oncology population, and to investigate whether intensity of treatment has similar associated with risk of VTE development in patients with and without CNS tumors., Methods: A retrospective population-based cohort study of pediatric oncology patients in Atlantic Canada was conducted. Data collected from medical records included demographics, cancer type, treatment, presence of central venous catheters (CVC), and presence of thrombosis. Treatment intensity was assessed using the intensity of treatment rating scale (ITR-3). Study period was from January 2000 to December 2017. SPSS version 24 was used for statistical analysis., Results: Of 1262 patients with pediatric cancer, 247 (19.6%) had CNS tumors. VTE occurred in significantly fewer (n = 5, 2%) patients with CNS tumors compared with patients with non-CNS cancers (n = 79, 7.8%) (p = 0.001). The ITR-3 scores did not differ significantly between the CNS and non-CNS groups (p = 0.638). In a multivariate logistic regression analysis, ITR-3 score was associated with VTE (odds ratio [OR]: 1.48, 95% CI: 1.2-1.9), while presence of CNS tumor was protective (OR: 0.26, 95% CI: 0.1-0.6)., Conclusions: We demonstrate that pediatric patients with CNS tumors experience a significantly lower incidence of VTE compared with patients with non-CNS cancer. An increase in the ITR-3 rating significantly increased the odds of developing VTE., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

In children under the age of 3 years, the most common solid tumors are brain tumors. Low grade astrocytomas represent 30-40 % of brain tumours in this age group. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with a low grade astrocytoma from 1990 to 2005 in Canada. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumors between 1990 and 2005. Cases of low grade astrocytoma were extracted from this data bank and their characteristics summarized. From the 579 cases in the data bank, 153 cases of low grade astrocytoma (26 %) were identified. The mean duration of symptoms prior to presentation was 13 weeks, and 53 % of patients underwent a greater than 90 % resection of their tumor, while 30 % underwent 10-90 % resection. Seventy-one percent of patients received no further therapy after surgery and of the 45 who received therapy following surgery, 43 received chemotherapy, and 5 received radiation therapy. Sixty-eight patients had recurrence or progression of their tumor. Eighty-seven percent of patients were alive at the time of the survey with a 2 year survival rate of 95.3 ± 1.8 %, 5 year survival rate of 93.1 ± 2.1 % and 10 year survival rate of 89.1 ± 2.8 %. The 5 year survival rate for Canadian children less than 36 months of age with a low grade astrocytoma was 93.0 ± 2.8 % which is similar to that for older children with this tumor.

The determination of optimal therapy for ependymoma (EP) in infants is ongoing. We describe the incidence, management and outcomes of Canadian infants with EP to discern potential future research questions. Of 579 cases registered in a national database of children <36 months of age diagnosed with a brain tumor from 1990 to 2005, inclusive, 75 (13 %) were EP. These cases were analyzed. A mean annual age-adjusted incidence rate of 4.6 per 100,000 children years was calculated. The male:female ratio was 1.77. Of the tumors, 80 % were infratentorial in location, 67 % were WHO grade II histology, and 29 % were metastatic at diagnosis. All patients underwent a surgical procedure. A complete resection of the tumor was achieved in 56 % of the cases; 43 % of these patients survive while 36 % of the patients with tumors less than completely resected survive. Initial therapy consisted of surgery alone in 23 % of patients, or surgery plus chemotherapy (37 %), radiation therapy (RT; 19 %), or both (21 %). Any use of RT increased with patient age. The 5-year EFS rates for patients in each of the four treatment groups was 22, 11.5, 46.2 and 64.8 %, respectively. For all patients the median survival was 63 ± 6 months and 5-year overall survival was 55 ± 6 %. Patients treated with surgery and chemotherapy alone were younger and had a lower rate of survival than older patients who were more often treated with radiation therapy containing regimens. Further study is needed to determine which patients are optimally served with these treatment modalities.

Children under the age of 3 with medulloblastoma have an inferior survival to older children with this disease. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with medulloblastoma from 1990 to 2005 in Canada. Ninety-six cases were identified with a median age at diagnosis of 19.5 months. Forty-seven percent of patients had a complete resection, 25% a 90-95% near complete resection, 20% an incomplete (10-90%) resection, and 3% biopsy only. Therapy consisted of chemotherapy (90%), high dose chemotherapy with stem cell rescue (13%), and radiation therapy (21%). The median survival time was 45 +/- 13.82 months. There was no significant difference in survival when comparing patients with <90% resection versus >90% resection, nor when comparing the presence of metastases versus their absence. There was a significant increase in survival time in patients who received radiation therapy compared to those who were not treated with this modality, as well as for those who were over 18 months at diagnosis compared to those under 18 months.

Introduction: Supratentorial primitive neuroectodermal tumors (SPNET) are rare tumors accounting for only 2.5% of childhood brain tumors. The purpose of this study was to describe the range of treatment regimens used to treat pediatric SPNET in Canada and to identify prognostic factors for overall survival in this population., Methods: This study was a retrospective clinical analysis of SPNET patients treated over the last 10 years in Canada. A questionnaire was developed and distributed to all institutions in Canada who treat pediatric patients. Data were collected for patients <19 years of age who were diagnosed and treated for SPNET between 1995 and 2005., Results: Data were obtained for 48 eligible patients. The stages of patients for whom complete data were provided were 80, 3, and 16% for metastatic stage M0, M1, and M2/3, respectively. The best responses to therapy included complete response in 44%, partial response in 8%, still on therapy in 2%, progressive disease in 31%, toxic death in 2%, and no therapy given in 12%. The 4-year survival was 37.7 +/- 7.6%. The factors associated with an increase in survival were the use of radiation therapy and chemotherapy, and age >2 years. Overall survival was not affected by metastatic disease at diagnosis, tumor site, or degree of initial resection., Conclusions: Survival is poor in SPNET patients but highest in those who received chemotherapy and radiation therapy. Further studies are needed to improve the survival of these patients.

Background and Purpose: Reports of secondary high-grade glioma (HGG) in survivors of childhood cancer are scarce. The aim of this study was to review the pattern of diagnosis, the treatment, and outcome of secondary pediatric HGG., Patients and Methods: We performed a multi-center retrospective study among the 17 paediatric institutions participating in the Canadian Pediatric Brain Tumour Consortium (CPBTC)., Results: We report on 18 patients (14 males, 4 females) treated in childhood for a primary cancer, who subsequently developed a HGG as a second malignancy. All patients had previously received radiation therapy +/- chemotherapy for either acute lymphoblastic leukaemia (n=9) or solid tumour (n=9). All HGG occurred within the previous radiation fields. At the last follow-up, 17 patients have died and the median survival time is 9.75 months., Conclusion: Although aggressive treatment seems to provide sustained remissions in some patients, the optimal management is still to be defined. Further documentation of such cases is necessary in order to better understand the pathogenesis, the natural history and the prevention of these tumours.