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Intrathecal therapy for the management of leptomeningeal metastatic disease: a scoping review of the current literature and ongoing clinical trials

Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing variable outcomes. We reviewed the therapeutic and toxicity profiles of ITT in LMD.

Methods

PubMed, EMBASE, Web-of-Science, and Scopus were searched following the PRISMA-ScR guidelines to include studies reporting ITT for LMD. Clinicaltrial.gov and Cochrane were searched to identify ongoing clinical trials.

Results

We included 27 published studies encompassing 2161 patients and 4 ongoing trials. LMD originated from brain metastases (85.5%), lymphomas (5.4%), high-grade gliomas (4.6%), medulloblastomas (2.3%), and leukemias (2.1%). LMD was mostly diagnosed with the co-presence of neurological-related symptoms and positive imaging and/or cerebrospinal fluid cytology (60.8%). The most common ITT agents were methotrexate (35.9%), cytarabine (21.9%), and thiotepa (8.2%), standalone or combined. Patients received a median of 6.5 ITT cycles (range, 1.0–71.0) via intraventricular (58.8%) or lumbar intrathecal (41.2%) routes. The Ommaya reservoir was implanted in 38.5% cases. Concurrent systemic chemotherapy (45.2%) and/or radiotherapy (30.6%) were used. After 1–3 cycles, 44.7% patients had improved clinical status and 29.9% converted into negative cerebrospinal fluid cytology. The most common ITT-related severe adverse events were neutropenia (6.5%), meningitis (5.2%) and encephalopathy (4.5%). Median freedom from progression was 2.4 months (range, 0.1–59.5) and median overall survival 5.5 months (range, 0.1–148.0).

Conclusion

Current ITT protocols are variable but effective and well-tolerated in LMD. Ongoing trials are investigating dose-limiting toxicity profiles and long-term overall survival. Future studies should analyze the therapeutic and safety profiles of ITT compared to newer systemic therapies.

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Fig. 1

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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All authors contributed to the study conception and design. The study was conceptualized and supervised by RSD and MV Material preparation, data collection and analysis were performed by PP, GW, AC, and CO The first draft of the manuscript was written by PP and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Palmisciano, P., Watanabe, G., Conching, A. et al. Intrathecal therapy for the management of leptomeningeal metastatic disease: a scoping review of the current literature and ongoing clinical trials. J Neurooncol 160, 79–100 (2022). https://doi.org/10.1007/s11060-022-04118-0

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