Treatment of young children with CNS-positive acute lymphoblastic leukemia without cranial radiotherapy

Background: Due to the long-term sequelae of cranial radiotherapy (CRT), contemporary treatment protocols for children with acute lymphoblastic leukemia (ALL) aim to limit the use of prophylactic CRT. For patients with central nervous system (CNS) involvement with ALL at diagnosis, the use of CRT remains common. Children \u3c5 years of age are a particularly challenging subgroup in whom the consequences of CRT can be devastating. Procedure: This study retrospectively describes the overall (OS) and event-free survival (EFS) of young children (1-5 years) who were treated for CNS-positive ALL at the Hospital for Sick Children between 2000 and 2013. Results: Of a total of 19 patients, two were treated with upfront CRT, both as part of the conditioning regimen prior to HSCT. All patients received intensification of CNS-directed chemotherapy by triple intra-thecal chemotherapy (84.2%), use of dexamethasone in induction (57.9%) and maintenance (66.7%), and high-dose methotrexate (77.8%). The OS was 84.2±8.4% and EFS was 79.0±9.4% with a median follow-up time of 4.3 years (range, 2.6-8.2). The cumulative incidence of CNS relapse was 5.2±5.1%. Conclusions: We conclude that omission of CRT from the treatment of young children with ALL involving the CNS is associated with acceptable survival and avoids potentially devastating late effects in this group

Low socioeconomic status is associated with worse survival in children with cancer: A systematic review

Background: While low socioeconomic status (SES) has been associated with inferior cancer outcome among adults, its impact in pediatric oncology is unclear. Our objective was therefore to conduct a systematic review to determine the impact of SES upon outcome in children with cancer. Methods: We searched Ovid Medline, EMBASE and CINAHL from inception to December 2012. Studies for which survival-related outcomes were reported by socioeconomic subgroups were eligible for inclusion. Two reviewers independently assessed articles and extracted data. Given anticipated heterogeneity, no quantitative meta-analyses were planned a priori. Results: Of 7,737 publications, 527 in ten languages met criteria for full review; 36 studies met final inclusion criteria. In low- and middle-income countries (LMIC), lower SES was uniformly associated with inferior survival, regardless of the measure chosen. The majority of associations were statistically significant. Of 52 associations between socioeconomic variables and outcome among high-income country (HIC) children, 38 (73.1%) found low SES to be associated with worse survival, 15 of which were statistically significant. Of the remaining 14 (no association or high SES associated with worse survival), only one was statistically significant. Both HIC studies examining the effect of insurance found uninsured status to be statistically associated with inferior survival. Conclusions: Socioeconomic gradients in which low SES is associated with inferior childhood cancer survival are ubiquitous in LMIC and common in HIC. Future studies should elucidate mechanisms underlying these gradients, allowing the design of interventions mediating socioeconomic effects. Targeting the effect of low SES will allow for further improvements in childhood cancer survival. © 2014 Gupta et al

BRAFV600E mutation in cutaneous lesions of patients with adult Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by the proliferation of pathologic Langerhans cells. The disease can develop in any age and can affect almost any organ. Cutaneous involvement is frequent in LCH. The recent demonstration of the activating, oncogenic BRAFV600E gene mutation in LCH samples strongly supports the neoplastic origin of the disease. OBJECTIVES: Our aim was to analyse the clinical data of the patients and whether BRAFV600E mutation is present in skin lesions of patients with adult onset LCH, and to investigate whether the BRAFV600E mutation status has any effect on the clinical presentation and the outcome of the disease. METHODS: We diagnosed and treated 15 adult LCH patients in the period of 1987-2012 and collected their clinical data. Three of our patients suffered from skin involvement and 12 patients had multiorgan disease (five patients out of the multisystem group died). Eleven formalin-fixed paraffin-embedded skin samples from 10 patients were available for BRAFV600E mutation analysis. RESULTS: Among the 11 examined samples, 6 contained the BRAFV600E mutation (54.5%). Our results indicate that in the adult group of LCH patients the presence of BRAFV600E mutation is similar to what was previously suggested in case of the childhood forms, at least as far as skin lesions are concerned. The BRAF mutation status of our patients does not seem to correlate with the extent and/or the outcome of the disease. CONCLUSION: Our results support the neoplastic origin of LCH and suggest that skin lesions of LCH are sufficient for the diagnosis of the disease and for assessing its BRAF status. In addition, analysis of BRAF status of patients with LCH can lead to the administration of new targeted therapies which may provide better disease control and prognosis

Retinal nerve fibre layer thinning is associated with worse visual outcome after optic neuritis in children with a relapsing demyelinating syndrome

AIM: Optic neuritis may be monophasic or occur as part of a relapsing demyelinating syndrome (RDS), such as multiple sclerosis, aquaporin-4 antibody (AQP4-Ab) neuromyelitis optical spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. The aims of this study were to test whether clinical, electrophysiological, and microstructural parameters differ in multiple-sclerosis-associated optic neuritis (MS-ON) and antibody-associated optic neuritis (Ab-ON); to identify the clinical and paraclinical characteristics of children suffering worse long-term visual outcome of RDS-optic neuritis; and to explore the relationship between RNFL thickness and clinical parameters in RDS-optic neuritis. METHOD: Forty-two children with optic neuritis were retrospectively studied: 22 with multiple sclerosis (MS-ON) and 20 with antibody-associated demyelination (Ab-ON: MOG-Ab=16 and AQP4-Ab=4). Clinical and paraclinical features were analysed. RESULTS: Complete recovery of visual acuity was reported in 25 out of 42 children; eight out of 38 (21%) suffered moderate or severe visual impairment (logarithm of the minimum angle of resolution [logMAR]>0.5) in their worse eye, including four out of 38 who were blind (logMAR>1.3) in their worse eye (two with multiple sclerosis, two with AQP4-Ab NMOSD). None of the children with MOG-Ab were blind. Recurrence of optic neuritis was more common in the Ab-ON group than the MS-ON group (15 out of 20 vs seven out of 22, p=0.007). Retinal nerve fibre layer (RNFL) thickness at baseline inversely correlated with visual acuity at final follow-up (r=-0.41, p=0.008). There was no significant relationship between the number of episodes of optic neuritis and mean RNFL (r=-0.08, p=0.628), nor any significant relationship between the number of episodes of optic neuritis and visual impairment (r=0.03, p=0.794). INTERPRETATION: In children with RDS, long-term visual impairment inversely correlated with RNFL thickness, but not with the number of relapses of optic neuritis. Optical coherence tomography may have a role in assessing children with optic neuritis to monitor disease activity and inform treatment decisions. WHAT THIS PAPER ADDS: Long-term visual impairment is reported in 40% of children with a relapsing demyelinating syndrome following optic neuritis. Relapse of optic neuritis, occurring more frequently in the non-multiple-sclerosis group. Retinal nerve fibre layer thinning is associated with worse visual outcome. Optical coherence tomography can be used alongside clinical parameters as an objective measure of neuroretinal loss

The Clinical Characteristics of Optic Neuritis in Korean Children

To study the clinical characteristics of optic neuritis in Korean children. A retrospective review of the medical charts of 20 patients who were diagnosed with optic neuritis before age 10 was conducted in this study. Data were collected on the demographics, clinical features, use of intravenous corticosteroids, neuroimaging, and diagnosis of multiple sclerosis. The mean age at diagnosis was 6.5 ± 1.8 years (range, 3 to 9 years). Seventeen patients (85%) were female, and 13 patients (65%) exhibited bilateral diseases. Visual acuity had decreased to ≤20 / 200 in 16 of the 20 patients, and recovered to ≥20 / 40 in 16 of the 20 patients. The mean duration between the worst visual acuity and 20 / 40 was 2.30 ± 2.91 months. Intravenous corticosteroid treatment was performed in 15 patients and exerted a beneficial effect on the visual outcomes. Disc swelling was observed in 75.8% of the affected eyes. Multiple sclerosis was diagnosed in five patients with a mean follow-up period of 21.9 ± 20.3 months. The presence of lesions in brain magnetic resonance images was identified as the most significant factor with regards to the occurrence of multiple sclerosis. In children with optic neuritis, a profound decrease in initial visual acuity and rapid recovery of visual acuity were confirmed. Corticosteroid treatment resulted in a beneficial effect on visual outcomes, but had no effect on the risk of multiple sclerosis. © 2011 The Korean Ophthalmological SocietyY

Training for Wellness in Pediatric Oncology: A Focus on Education and Hidden Curricula

Pediatric oncologists have the privilege of caring for children and families facing serious, often life-threatening, illnesses. Providing this care is emotionally demanding and associated with significant risks of stress and burnout for oncologists. Traditional approaches to physician burnout and wellbeing have not emphasized the potential roles of education and training in mitigating this stress. In this commentary, we discuss the contribution that education, particularly in the areas of palliative and psychosocial oncology, can make in preparing oncologists for the work that they do. We argue that by adequately providing oncologists with the skills they need for their work, we can reduce their risk of burning out. We also discuss the importance of paying attention to hidden and formal curricula to ensure that messages provided in formal education programs are supported by informal training experiences