Leptomeningeal malignancy of childhood: sharing learning between childhood leukaemia and brain tumour trials

Walker, David A; Meijer, Lisethe; Coyle, Beth; Halsey, Christina

Abstract

Leptomeningeal malignancy complicates childhood cancers, including leukaemias, brain tumours, and solid tumours. In leukaemia, such malignancy is thought to invade leptomeninges via the vascular route. In brain tumours, dissemination from the primary tumour, before or after surgery, via CSF pathways is assumed; however, evidence exists to support the vascular route of dissemination. Success in treating leptomeningeal malignancy represents a rate-limiting step to cure, which has been successfully overcome in leukaemia with intensified systemic therapy combined with intra-CSF therapy, which replaced cranial radiotherapy for many patients. This de-escalated CNS-directed therapy is still associated with some neurotoxicity. The balanced benefit justifies exploration of ways to further de-escalate CNS-directed therapy. For primary brain tumours, standard therapy is craniospinal radiotherapy, but attendant risk of acute and delayed brain injury and endocrine deficiencies compounds post-radiation impairment of spinal growth. Alternative ways of treating leptomeninges by intensifying drug therapy delivered to CSF are being investigated—preliminary evidence suggests improved outcomes. This Review seeks to describe methods of intra-CSF drug delivery and drugs in use, and consider how the technique could be modified and additional drugs might be selected for this route of administration.

Citation

Walker, D. A., Meijer, L., Coyle, B., & Halsey, C. (2020). Leptomeningeal malignancy of childhood: sharing learning between childhood leukaemia and brain tumour trials. Lancet Child and Adolescent Health, 4(3), 242-250. https://doi.org/10.1016/s2352-4642%2819%2930333-5

• Journal Article Type: Article
• Acceptance Date: Jan 10, 2020
• Online Publication Date: Jan 17, 2020
• Publication Date: 2020-03
• Deposit Date: Mar 6, 2020
• Publicly Available Date: Jul 18, 2020
• Journal: The Lancet Child & Adolescent Health
• Electronic ISSN: 2352-4650
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 3
• Pages: 242-250
• DOI: https://doi.org/10.1016/s2352-4642%2819%2930333-5
• Public URL: https://nottingham-repository.worktribe.com/output/4097345
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S2352464219303335
• Additional Information: This article is maintained by: Elsevier; Article Title: Leptomeningeal malignancy of childhood: sharing learning between childhood leukaemia and brain tumour trials; Journal Title: The Lancet Child & Adolescent Health; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/S2352-4642(19)30333-5; Content Type: article; Copyright: © 2020 Elsevier Ltd. All rights reserved.