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Leptomeningeal disease in glioblastoma: endgame or opportunity?



Glioblastoma is an aggressive cancer with a notoriously poor prognosis. Recent advances in treatment have increased overall survival, though this may be accompanied by an increased incidence of leptomeningeal disease (LMD). LMD carries a particularly severe prognosis and remains a late stage manifestation of glioblastoma without satisfactory treatment. The objective of this review is to survey the literature on treatment of LMD in glioblastoma and to more fully characterize the current therapeutic strategies.


The authors performed a systematic review following PRISMA criteria on PubMed and OVID databases. Articles that included adult patients with LMD from glioblastoma were retrieved and reviewed.


LMD in glioblastoma patients is increasing in incidence, with reports of up to 21%. The overall survival without treatment is alarmingly brief, with patients surviving between 1.6–3.8 months. All studies showed that treatment does improve overall survival significantly, increasing to 11.7 months in one study. However, no one adjuvant or surgical therapy has been shown to improve survival in LMD significantly over another. Direct treatment methods include chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation. Hydrocephalus is a complication in LMD that can be treated with ventriculoperitoneal shunt placement, however treating hydrocephalus and delivering intrathecal chemotherapy is a challenge.


Though evidence remains lacking and there is no consensus, treatments show a trend towards improving survival and should be considered on a case-by-case basis. Further studies are necessary in the pursuit of a standard of care.

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Leptomeningeal disease


Cerebrospinal fluid


Karnofsky performance status


Whole brain radiotherapy




Vascular endothelial growth factor


Intrathecal methotrexate




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All authors contributed to the study conception and design. Data collection and analysis were performed by SA and EG. Statistical consultation was provided by AJD. The first draft of the manuscript was written by SA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Simon J. Hanft.

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Akmal, S., Ginalis, E.E., Patel, N.V. et al. Leptomeningeal disease in glioblastoma: endgame or opportunity?. J Neurooncol 155, 107–115 (2021).

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  • Glioblastoma
  • Leptomeningeal disease
  • Leptomeningeal metastasis
  • Neuro-oncology