Letter to the Editor. Standardization of dexamethasone utility in pediatric neuro-oncosurgery

Scott R. Morrison MBChB, BMedSci (Hons) and Chandrasekaran Kaliaperumal MBBS, DipMedEd, FEBNS, FRCSI, FRCSEd (Neurosurgery)
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  • NHS Lothian, Edinburgh, Scotland
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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):261273.

    • Search Google Scholar
    • Export Citation
  • 2

    Kofman S, Garvin JS, Nagamani D. Treatment of cerebral metastases from breast carcinoma with prednisolone. JAMA. 1957;163(16):14731476.

    • Search Google Scholar
    • Export Citation
  • 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):103114.

    • Search Google Scholar
    • Export Citation
  • 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):e493e503.

    • Search Google Scholar
    • Export Citation
  • 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; 1990:175186.

    • Search Google Scholar
    • Export Citation
  • 6

    Koehler PJ. Use of corticosteroids in neuro-oncology. Anticancer Drugs . 1995;6(1):1933.

  • 7

    Stuart FA, Segal TY, Keady S. Adverse psychological effects of corticosteroids in children and adolescents. Arch Dis Child . 2005;90(5):500506.

    • Search Google Scholar
    • Export Citation
  • 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):279284.

    • Search Google Scholar
    • Export Citation
  • 9

    Glaser AW, Buxton N, Walker D. Corticosteroids in the management of central nervous system tumours. Arch Dis Child . 1997;76(1):7678.

    • Search Google Scholar
    • Export Citation
  • 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):s502s503.

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    • Export Citation
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  • Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA

Response

Drs. Morrison and Kaliaperumal not only make a good point regarding the lack of standardization for dexamethasone dosing in pediatric neuro-oncology but also provide an interesting historical background. The lack of standardization of dexamethasone dosing in children is beyond the scope of our review article given the lack of solid data, but is certainly a topic of significant relevance for the management of pediatric brain tumors. The use of dexamethasone in children is empirically based on the adult experience, adjusted for patients’ weight or body surface area and according to response to treatment. As the authors note, the dosing of dexamethasone in children continues to be based on the clinical judgment of the treating neurosurgeon and/or neuro-oncologist. Except for immunotherapy studies, which often have strict limits for the dose of corticosteroids as an eligibility criterion, dosing parameters are usually left to the discretion of the clinical team in the context of supportive care.

Recent data suggest that antiangiogenic agents, such as bevacizumab, or modulation of upstream signaling mediators in the corticosteroid release pathway may minimize the dexamethasone dosing required for symptomatic improvement.1,2 In view of the poor prognosis of many types of childhood brain tumors that often warrant corticosteroid therapy for symptom management, such as diffuse intrinsic pontine gliomas and other high-grade neoplasms, the focus of contemporary trials has been on testing strategies that may improve outcome, rather than on comparing corticosteroid dosing approaches. As noted by the authors, an electronic survey on dexamethasone dosing could identify common practices but would not necessarily pinpoint the optimal dosing strategy.

References

  • 1

    Levin VA, Bidaut L, Hou P, Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Bio Phys. 2011;79(5):14871495.

    • Search Google Scholar
    • Export Citation
  • 2

    Recht L, Mechtler LL, Wong ET, Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy. J Clin Oncol. 2013;31(9):11821187.

    • Search Google Scholar
    • Export Citation

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Contributor Notes

Correspondence Scott R. Morrison: scott.x.morrison@nhslothian.scot.nhs.uk.

INCLUDE WHEN CITING Published online February 5, 2021; DOI: 10.3171/2020.11.PEDS20842.

Disclosures The authors report no conflict of interest.

  • 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):261273.

    • Search Google Scholar
    • Export Citation
  • 2

    Kofman S, Garvin JS, Nagamani D. Treatment of cerebral metastases from breast carcinoma with prednisolone. JAMA. 1957;163(16):14731476.

    • Search Google Scholar
    • Export Citation
  • 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):103114.

    • Search Google Scholar
    • Export Citation
  • 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):e493e503.

    • Search Google Scholar
    • Export Citation
  • 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; 1990:175186.

    • Search Google Scholar
    • Export Citation
  • 6

    Koehler PJ. Use of corticosteroids in neuro-oncology. Anticancer Drugs . 1995;6(1):1933.

  • 7

    Stuart FA, Segal TY, Keady S. Adverse psychological effects of corticosteroids in children and adolescents. Arch Dis Child . 2005;90(5):500506.

    • Search Google Scholar
    • Export Citation
  • 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):279284.

    • Search Google Scholar
    • Export Citation
  • 9

    Glaser AW, Buxton N, Walker D. Corticosteroids in the management of central nervous system tumours. Arch Dis Child . 1997;76(1):7678.

    • Search Google Scholar
    • Export Citation
  • 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):s502s503.

    • Search Google Scholar
    • Export Citation
  • 1

    Levin VA, Bidaut L, Hou P, Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Bio Phys. 2011;79(5):14871495.

    • Search Google Scholar
    • Export Citation
  • 2

    Recht L, Mechtler LL, Wong ET, Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy. J Clin Oncol. 2013;31(9):11821187.

    • Search Google Scholar
    • Export Citation

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