Neuroendocrine sequelae common after paediatric optic gliomas

By Eleanor McDermid, Senior medwireNews Reporter

Neuroendocrine sequelae are common following paediatric low-grade gliomas affecting the optic pathway, hypothalamus and suprasellar areas (OP/HSGs) and are influenced by tumour location and treatment choice, a study shows.

Twenty-year overall survival was high in the cohort of 166 children, at 81.0%, but endocrine event-free survival (EEFS) was just 20.8%. Most patients had their first endocrine event about a year after diagnosis, although one patient had their first event more than 14 years later.

“Thus, minimizing future endocrine, visual and cognitive morbidity remains an important therapeutic goal in managing these tumors”, say the researchers.

Progression-free survival was also fairly low, they report, at 47.2%, indicating “that the optimal treatment strategy for these benign lesions remains elusive”.

Hypothalamic involvement predicted reduced EEFS more strongly than did receipt of primary radiotherapy, and this remained the case for all individual endocrinopathies except for growth hormone deficiency and insulin resistance. This suggests that tumour mass causes hypothalamo-pituitary injury, which is then exacerbated in the event of progression, say Hoong-Wei Gan (University College London Institute of Child Health, UK) and co-researchers.

Radiotherapy “has long been assumed to cause greater neuroendocrine toxicity” than chemotherapy, but of the nine individual endocrinopathies studied, radiotherapy was significantly associated only with four (growth hormone deficiency, gonadotropin deficiency, adrenocorticotropic hormone deficiency and insulin resistance).

The researchers noted a tendency for reduced EEFS over successive treatment eras, which spanned 1980 to 2010, particularly for growth hormone deficiency which was the most common endocrinopathy overall and was a significant 2.48-fold more likely to occur in patients treated in 2005–2010 relative to 1980–1996.

The team describes this trend as “concerning given the lack of a corresponding improvement in survival”, and suggests that it may be due to physicians eschewing primary surgery and radiotherapy in favour of chemotherapy.

“[I]n aiming to improve long-term outcomes for OP/HSGs, there is a precarious balance between preventing disease progression and minimizing long-term treatment toxicity”, Gan and team observe.

But in a subcohort of 63 patients with biopsy-proven OP/HSGs, primary chemotherapy was independently associated with reduced, and primary surgery with increased, progression-free survival.

“We thus postulate that failure of a first-line chemotherapeutic strategy in preventing OP/HSG progression necessitates multiple salvage surgical or radiotherapeutic interventions which can, together with tumor growth, compound neuroendocrine morbidity”, write Gan et al in The Journal of Clinical Endocrinology & Metabolism.

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