TO THE EDITOR: We read with great interest the article by Pollack and colleagues1 (Pollack IF, Agnihotri S, Broniscer A. Childhood brain tumors: current management, biological insights, and future directions. 75th Anniversary Invited Review Article. J Neurosurg Pediatr. 2019;23[3]:261–273). It is an article deserving of praise, covering novel treatments in pediatric brain tumors. One thought occurring while reading was that, despite the excellent work on novel treatments, with trials assessing best dosing and how these should be implemented, there is still no guidance regarding the use of dexamethasone in the pediatric central nervous system (CNS) tumor population.
The benefit from corticosteroids in managing symptoms related to CNS tumors is well known, and their use is widespread, with dexamethasone being the most common agent.2,3 It has been over 60 years since Kofman et al. reported on these benefits.2 In this 60-year time span, adult dosing recommendations have been suggested, with relative consensus in dosing.4 In pediatrics, however, no such consensus exists. We believe introducing dosing guidelines for dexamethasone in pediatric CNS tumors would be appreciably useful.
Dexamethasone is invaluable but carries significant side effects,5,6 particularly in pediatric patients, with growth retardation and psychological effects noted alongside the more common gastrointestinal side effects.7 Studies have also proven that the incidence of adverse effects is directly related to dosage.8 While the literature is heterogeneous, numerous studies in adults have noted no significant benefit for symptoms with increased doses, outside the cases of severe disease.3 Most significant, and concerning, of all is that current pediatric dexamethasone use in CNS tumors is based on “conventional wisdom and use.”9
Reviewing the literature, one finds a number of articles noting the paucity of evidence on this topic, with Glaser et al. discussing the lack of standardization of pediatric dosing and the possible ill effects back in 1997.9 Curry et al. noted no standardized dosing regimen for dexamethasone in pediatrics and therefore attempted a randomized controlled trial in a number of Canadian institutions trialing low-dose versus higher-dose dexamethasone in children with intracranial tumors.10 Because of the low recruitment numbers, no definitive conclusion could be inferred. However, their study confirmed 80% of the institutions had no local standard for dexamethasone and wide dose variations between institutions. The literature highlights this as a global issue, drawing interest from numerous professionals, including pediatric neuro-oncologists.
Dexamethasone was introduced prior to the stringent clinical trials that are commonplace today—and noted in Pollack and colleagues’ work—allowing it to become used with significant variety and lack of standardization. A randomized controlled trial utilizing different methods of administration, as well as differing doses, would have great utility. It would be valuable to investigate tapering periods, as the less time that this population spends on steroids, the better.
We acknowledge the variety of the pediatric CNS and note that management is often tailored to each child. However, this should not discourage considering the development of guidelines here. We hope our international colleagues share our opinion on developing guidelines for dexamethasone in the pediatric population, allowing the most effective treatment with the most acceptable side effect profile. In the current circumstances, an electronic survey would be a good starting point to obtain data on the individual practice of neurosurgical and pediatric oncology teams, with subsequent collaboration between teams nationally and internationally.
Disclosures
The authors report no conflict of interest.
References
- 1↑
Pollack IF, Agnihotri S, Broniscer A. Childhood brain tumors: current management, biological insights, and future directions. 75th Anniversary Invited Review Article. J Neurosurg Pediatr. 2019;23(3):261–273.
- 2↑
Kofman S, Garvin JS, Nagamani D. Treatment of cerebral metastases from breast carcinoma with prednisolone. JAMA. 1957;163(16):1473–1476.
- 3↑
Ryken TC, McDermott M, Robinson PD, The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):103–114.
- 4↑
Kostaras X, Cusano F, Kline GA, Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline. Curr Oncol. 2014;21(3):e493–e503.
- 5↑
Deutsch M, Albright AL. Surgery in the management of childhood brain tumors. In: Deutsch M, ed. Management of Childhood Brain Tumors . Kluwer Academic Publishers; 1990:175–186.
- 7↑
Stuart FA, Segal TY, Keady S. Adverse psychological effects of corticosteroids in children and adolescents. Arch Dis Child . 2005;90(5):500–506.
- 8↑
Walsh LJ, Wong CA, Oborne J, Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax. 2001;56(4):279–284.
- 9↑
Glaser AW, Buxton N, Walker D. Corticosteroids in the management of central nervous system tumours. Arch Dis Child . 1997;76(1):76–78.
- 10↑
Curry S, Dutton J, Awrey S, Dexamethasone dosing in children with brain tumours: an unresolved problem. PO-177. Pediatr Blood Cancer. 2018;65(Suppl 2):s502–s503.
