Anne-Sophie Carret

Central nervous system atypical teratoid rhabdoid tumours: The Canadian Paediatric Brain Tumour Consortium experience

BACKGROUND Atypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional experiences (1-4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors. PATIENTS AND METHODS A national retrospective study of children ⩽18years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review. RESULTS There were 50 patients (31 males; median age at diagnosis of 16.7months). Twelve patients were >36months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation. Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5months (0-32). The median survival time of the entire cohort was 13.5months (1-117.5months). Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2years overall survival (OS): 60%±12.6 versus 21.7%±8.5, p=0.03). HDC conferred better outcome (2years OS 47.9%±12.1 versus 27.3%±9.5, p=0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation. CONCLUSION The outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.

Carboplatin Hypersensitivity Reaction in Pediatric Patients With Low-grade Glioma : A Canadian Pediatric Brain Tumor Consortium Experience

Carboplatin‐based regimens have demonstrated activity in pediatric patients with low‐grade glioma (LGG). However, carboplatin hypersensitivity reaction (Cb HSR) represents a common and limiting factor for the continuation of therapy.

Remote control of the permeability of the blood-brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery.

Despite advances in neurology, drug delivery to the brain remains a substantial challenge. This is mainly due to the insurmountable and selective nature of the blood-brain barrier (BBB). In this study, we show that the thermal energy generated by magnetic heating (hyperthermia) of commercially available magnetic nanoparticles (MNPs) in the brain capillaries of rats can transiently increase barrier permeability. Here, the fluorescent Evans Blue (EB) dye was used to verify the BBB integrity. Results indicate a substantial but reversible opening of the BBB where hyperthermia is applied. Also, in this investigation, analysis of CD68 immunoreactivity, an indicator of inflammation, implies that this technique is not associated with any inflammation. We have previously investigated theranostic (therapeutic and diagnostic) capabilities of the MNPs, therefore, the findings presented in this investigation are particularly encouraging for a novel targeted drug delivery system to the brain.

Long-term therapy with aerosolized ribavirin for parainfluenza 3 virus respiratory tract infection in an infant with severe combined immunodeficiency.

Abstract:  We report the case of an infant with severe combined immunodeficiency who was presented with PIV3 infection. Aerosolized ribavirin was administered for 10 months until the child gained a functional immune system through an allogeneic hematopoietic stem cell transplant and cleared PIV3 infection. No adverse effect was observed in the child and in healthcare personnel, with a follow‐up of three years. Despite the burden of aerosolized administration, early and prolonged administration of aerosolized ribavirin was feasible, well tolerated, and safe for the patient and the caregivers. This is a case report and no definite conclusions can be drawn. However, our experience suggests that prolonged aerosolized ribavirin administration should be considered for the treatment of PIV3 infection in the context of primary immunodeficiency, where there is no currently available alternative treatment, until a functional immune system is gained.

Incidence of platinum-induced ototoxicity in pediatric patients in Quebec.

The antineoplastic agents cisplatin and carboplatin are widely‐used and highly‐effective against a variety of pediatric cancers. Unfortunately, ototoxicity is a frequently encountered side effect of platinum‐based chemotherapy. There is currently no treatment or prevention for platinum‐induced ototoxicity and development of hearing loss may lead to devastating consequences on the quality of life of pediatric cancer survivors. The objective of this study is to determine the incidence of platinum‐induced ototoxicity in a large series of pediatric patients and to evaluate the incidence of progression of ototoxicity after completion of treatment.

Visual acuity of children treated with chemotherapy for optic pathway gliomas

Chemotherapy is the most common primary treatment modality for pediatric optic pathway gliomas (OPGs). Due to the risk of severe visual impairment, visual acuity (VA) has become a clinical parameter of fundamental importance for children with OPGs. Despite this reality, most studies omit crucial information necessary for analysis of the effect of chemotherapy on VA in patients with cerebral gliomas. The principal goal of this study was to determine the immediate and long‐term visual outcome of children treated first with chemotherapy for OPGs.

Nurses provide valuable proxy assessment of the health-related quality of life of children with Hodgkin disease†

We prospectively compared the proxy reporting of health‐related quality of life (HRQL) by parents and nurses of children with Hodgkin disease to see how well they correlated with the childrens report.

Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single‐Bone CNS‐Risk Lesions: A Multi‐Institutional Retrospective Study

Children with Langerhans cell histiocytosis (LCH) and single‐bone CNS‐risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS‐ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients.

EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a Canadian Pediatric Brain Tumor Consortium study.

The cure rate for childhood intracranial ependymoma is approximately 70% in the setting of a gross total resection followed by radiation, but management remains challenging in patients with residual disease. Therefore, robust biomarkers are needed to guide the development of new targeted therapy. The authors evaluated the expression of several biomarkers in pediatric intracranial ependymoma and observed that the expression of enhancer of zeste homolog 2 (EZH2), a polycomb complex protein involved in epigenetic regulation of gene expression, was independently associated with poor survival.

Stability and Repeatability of the Distress Thermometer (DT) and the Edmonton Symptom Assessment System-Revised (ESAS-r) with Parents of Childhood Cancer Survivors.

Objective Parents report psychological distress in association with their childs cancer. Reliable tools are needed to screen parental distress over the cancer trajectory. This study aimed to estimate the stability and repeatability of the Distress Thermometer (DT) and the Depression and Anxiety items of the Edmonton Symptom Assessment System-revised (ESAS-r-D; -A) in parents of children diagnosed with cancer. Methods Fifty parents (28 mothers, median age = 44) of clinically stable survivors of childhood solid and brain tumours completed questionnaires about their own distress (DT, ESAS-r-D; -A, Brief Symptom Inventory-18: BSI-18, Patient Health Questionnaire-9: PHQ-9, Generalized Anxiety Disorder-7: GAD-7) and their children’s quality of life (QoL; Peds Quality of Life: PedsQL) twice, with a month interval between the two assessments. At retest, parents also evaluated life events that occurred between the two time points. Hierarchical regressions explored moderators for the temporal stability of test measures. Results Stability estimates were ICC = .78 for the DT, .55 for the ESAS-r-D, and .47 for the ESAS-r-A. Caseness agreement between test and retest was substantial for the DT, fair for the ESAS-r-D, and slight for the ESAS-r-A. Repeatability analyses indicated that the error range for the DT was more than 2 pts below/above actual measurement, whereas it was more than 3 pts for the ESAS-r-A, and 2.5 for the ESAS-r-D. Instability of the DT could be explained by changes in children’s physical QoL, but not by other components of QoL or life events. No moderators of stability could be identified for the ESAS-r items. Conclusions The DT appears to be a fairly stable measure when the respondents condition is stable yet with a relatively wide error range. Fluctuations in distress-related constructs may affect the temporal stability of the DT. The lower stability of ESAS-r items may result from shorter time-lapse instructions resulting in a greater sensitivity to change. Findings support future research on the DT as a reliable instrument in caregivers.