J Korean Neurosurg Soc.  2021 Jul;64(4):631-643. 10.3340/jkns.2020.0300.

Cerebrospinal Fluid Profiles and Their Changes after Intraventricular Chemotherapy as Prognostic or Predictive Markers for Patients with Leptomeningeal Carcinomatosis

• Kwon JW
• Shim Y
• Gwak HS
• Park EY
• Joo J
• Yoo H
• Shin SH

• KMID: 2517695
• DOI: http://doi.org/10.3340/jkns.2020.0300

Abstract

Objective
: Here, we evaluated whether cerebrospinal fluid (CSF) profiles and their changes after intraventricular chemotherapy for leptomeningeal carcinomatosis (LMC) could predict the treatment response or be prognostic for patient overall survival (OS) along with clinical factors.
Methods
: Paired 1) pretreatment lumbar, 2) pretreatment ventricular, and 3) posttreatment ventricular samples and their CSF profiles were collected retrospectively from 148 LMC patients who received Ommaya reservoir installation and intraventricular chemotherapy. CSF profile changes were assessed by calculating the differences between posttreatment and pretreatment samples from the same ventricular compartment. CSF cell counts were further differentiated into total and other based on clinical laboratory reports.
Results
: For the treatment response, a decreased CSF ‘total’ cell count tended to be associated with a ‘controlled’ increase in intracranial pressure (ICP) (p=0.059), but other profile changes were not associated with either the control of increased ICP or the cytology response. Among the pretreatment CSF profiles, lumbar protein level and ventricular cell count were significantly correlated with OS in univariable analysis, but they were not significant in multi-variable analysis. Among CSF profile changes, a decrease in ‘other’ cell count showed worse OS than ‘no change’ or increased groups (p=0.001). The cytological response was significant for OS, but the hazard ratio of partial remission was paradoxically higher than that of ‘no response’.
Conclusion
: A decrease in other cell count of CSF after intraventricular chemotherapy was associated with poor OS in LMC patients. We suggest that more specific CSF biomarkers of cancer cell origin are needed.

Keyword

Cerebrospinal fluid; Spinal puncture; Injections, Intraventricular; Meningeal carcinomatosis; Prognosis

Figure

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  Fig. 1. Flow diagram of patient selection. LMC : leptomeningeal carcinomatosis, CSF : cerebrospinal fluid.

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  Fig. 2. Interaction plot depicting changes in the (A) total cell count, (B) other cell count, and (C) protein level between pretreatment and posttreatment ventricular CSF samples. After the intraventricular chemotherapy, total cell count and ‘other cell count’ were decreased significantly (to mean 7.8 and 2.6 cells/mm3, respectively). In contrast to the CSF cell count, the CSF protein level was significantly increased after the treatment (to 48.2 mg/dL, p=0.014). See details in the Results section. CSF : cerebrospinal fluid.

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  Fig. 3. Kaplan-Meier plot of patient overall survival according to variables that were significant in the multivariable analysis : (A) age (<60 vs. ≥60 years), (B) rounds of intraventricular methotrexate administration (<5 vs. ≥5), (C) CSF cytology conversion, and (D) change in the CSF cell count (other). MTX : methotrexate, CSF : cerebrospinal fluid.

Reference

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