Abstract
Simple SummarySerious, poorly understood health issues affect young children with optic pathway tumours. We studied the risk of developing life-limiting hormonal, metabolic, and neurobehavioural disorders by tumour position, recurrence, and treatment, in those diagnosed under 3 years. We found the highest risk for future complex health issues in those presenting with failure to thrive, under one year of age, and/or a tumour involving a deep midbrain area called the hypothalamus. Time, repeated tumour growth, and salvage therapies (radiotherapy, surgery) contributed. We highlight the need for a better understanding of tumour-induced midbrain injury and for neurobehavioural and hormonal support to inform rehabilitation in the growing years, during and beyond cure, to optimise quality of life for these survivors and their families. This might inform oncology treatment strategies and determine new areas for support and collaborative neuroscience research in this high survival group.Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies.
Highlights
Paediatric low-grade gliomas are the most common type of central nervous system (CNS) tumours in children [1,2,3]
The remaining 90 were diagnosed with optic pathway and hypothalamic gliomas (OPHGs) at a median inter-quartile range (IQR) age of 1.84 (0.83–2.51) (0.06–3) years and followed for 9.5 (4–12.5) (0.5–25.0) years until aged 10.8 (5.7–14.2) (0.6–26.3) years; one-third (30: 33.3%) were under 1 year of age at diagnosis, of whom almost all (26/30, 86.7%) had post-chiasmatic and hypothalamic (28/30, 93.3%) involvement; the last feature was uniquely associated with diencephalic syndrome (DS) (27/90: 30%) and raised intracranial pressure (RICP) (22/90: 24%)
In this longitudinal study of 90 infants and young children diagnosed with OPHG before their third birthday and followed for a median of 9.5 but up to 25 years, we report the long-term neuroendocrine and metabolic morbidity of this very young population as it evolves with developmental age, tumour location, and disease course
Summary
Paediatric low-grade gliomas (pLGGs) are the most common type of central nervous system (CNS) tumours in children [1,2,3]. Around 30–50% of pLGGs affect diencephalic structures—the optic nerves, chiasm, tracts, hypothalamus, and suprasellar midline—and are collectively termed optic pathway and hypothalamic gliomas (OPHGs) [4] Their benign histology belies their often aggressive behaviour and recurrent treatments imposed in attempts to preserve vision, whilst any associated hypothalamic injury has not been possible to characterise alongside attempts to cure. The hypothalamic tumour location predicts the speed of onset of neuroendocrine deficits [9] and increases the incidence of anterior pituitary deficits and obesity [4] Those youngest at presentation and those with hypothalamic involvement have the poorest long-term overall survival (OS), progression-free survival (PFS), and clinical morbidity [4,9,16]. We aimed to study in detail the history of the evolution of hypothalamic quality of survival neuroendocrine, metabolic, and neurobehavioural outcomes in this very young population, against a background of increasing, repeated treatments cycles, to quantify the extent of—and ascertain which disease and treatment factors predicated—long-term morbidity outcomes that limit the quality of life
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