The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials

Lina Marenco-Hillembrand, Michael A. Bamimore, Julio Rosado-Philippi, Blake Perdikis, David N. Abarbanel, Alfredo Quinones-Hinojosa, Kaisorn L. Chaichana, Wendy J. Sherman

Research output: Contribution to journalReview articlepeer-review


Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5–15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2–6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982–2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments.

Original languageEnglish (US)
Article number685
Issue number3
StatePublished - Feb 2023


  • carcinomatous meningitis
  • clinical trial
  • leptomeningeal cancer
  • neoplastic meningitis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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