Introduction: Low-grade gliomas (LGGs) are the commonest benign childhood brain tumour and typically affect the optic tracts, chiasm and suprasellar diencephalon, thus potentially causing serious neuroendocrine deficits from tumour mass or treatment effects. In the absence of any major studies, we sought to comprehensively evaluate patient-, disease- and treatment-related risk factors for neuroendocrine morbidity in a large single-centre survivor cohort treated by varied, primarily non-surgical strategies over 30 years.
Methods: Retrospective case note analysis of the first 96 randomly audited patients with optic pathway and diencephalic LGGs diagnosed between 19802010 at Great Ormond Street Hospital by multivariate Cox and linear regression.
Results: Patients were of median age 5.15 (range 0.1815.07) years at diagnosis and followed up for a median of 6.57 (0.2526.12) years. 81.2% had midline suprasellar tumours of which 37.5% were hypothalamic. Five year overall survival, progression-free survival (PFS) and endocrine event-free survival (EEFS) were 96.9, 68.8 and 50.0% respectively. However, EEFS continued to fall up to 15 years from diagnosis, being independently reduced by hypothalamic involvement (P=0.002) and grade II histology (P=0.003) more than radiotherapy (P=0.028). The number of deficits (endocrine morbidity score) however was increased by radiotherapy (P=0.000) rather than hypothalamo-chiasmatic tumour position (P=0.042). GH deficiency was most frequent (36.5%), followed by central precocious puberty (20.8%), TSH deficiency (13.5%), ACTH deficiency (12.5%), LH/FSH deficiency (10.4%), and hyperprolactinaemia (7.3%). Five patients, all with hypothalamic involvement, suffered with salt-water balance disorders (one cerebral salt-wasting, two SIADH and two DI); 4/5 of these were postoperative (three biopsied only and one debulked).
Conclusion: This very long term multivariate analysis of detailed endocrine morbidity in a rare LGG survivor cohort provides new evidence to suggest hypothalamic tumour position is more important than irradiation in the incidence of endocrinopathies, and challenges the perception that surgery is less neurotoxic, especially in the diencephalic area where even minor surgical intervention such as biopsies may result in significant posterior pituitary dysfunction.
07 - 09 Nov 2012
British Society for Paediatric Endocrinology and Diabetes