Comprehensive Analysis of Leptomeningeal Metastasis in IDH Wild-Type Glioblastoma

In this article published in the journal “Neuro-Oncology,” the research team starting in 2024 delves into the incidence, risk factors, and prognosis of leptomeningeal metastases (LM) in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma. This study was jointly conducted by scholars Yae Won Park from Yonsei University College of Medicine in Seoul and Rajan Jain from New York University Grossman School of Medicine.

Background and Research Objectives

Leptomeningeal metastasis is a severe complication of IDH wild-type glioblastoma with a dire prognosis. Reports indicate that its incidence varies significantly, generally considered a relatively rare manifestation in clinical practice, with incidence rates ranging from 3.8% to 6.9%. However, due to advances in diagnostic technology, particularly with high-sensitivity imaging tools, this number might be underestimated. Cerebrospinal fluid (CSF) cytology is considered the “gold standard” for LM diagnosis; however, its sensitivity is low and it is invasive. Magnetic resonance imaging (MRI), on the other hand, serves as a non-invasive diagnostic tool. Recent studies have shown that post-contrast fluid-attenuated inversion recovery (FLAIR) imaging performs excellently in LM detection. Nevertheless, studies assessing the true incidence of LM in IDH wild-type glioblastoma patients using post-contrast FLAIR imaging are still lacking. This research aims to provide a comprehensive analysis of the incidence, risk factors, and prognosis of LM in IDH wild-type glioblastoma patients, providing a reference for clinical diagnosis of LM.

Research Methods

Subjects and Materials

The study sample included 828 IDH wild-type glioblastoma patients diagnosed at Yonsei University College of Medicine between 2005 and 2022. All patients met the following criteria: 1) histopathologically confirmed IDH wild-type glioblastoma; 2) known MGMT methylation status; 3) age ≥ 18 years; and 4) baseline MRI conducted before the initial surgery, including post-contrast FLAIR imaging.

MRI Diagnosis and Data Analysis

The research team used baseline preoperative MRI, including preoperative and postoperative FLAIR images, to determine whether patients had LM. LM was defined as linear or nodular leptomeningeal or ependymal enhancement and cranial nerve root enhancement on brain or spinal MRI, with or without hydrocephalus. MRI images were independently reviewed by two experienced neuroradiologists and further confirmed through patient clinical records and pathological reports. To improve image quality, the team pre-processed the images using advanced normalization tools (ANTs) and high-quality deep learning algorithms such as HD-Glio.

Statistical Analysis

Significant variables were used for multivariate analysis. Survival analysis was performed using the Kaplan-Meier method to compare overall survival (OS) between patients with and without LM. All statistical analyses were conducted using SPSS, with a significance level set at p < 0.05.

Research Results

Basic Characteristics and LM Incidence

The median age of the subjects was 62 years, with 494 males and 334 females, and a median KPS score of 90. In this population, the overall incidence of LM was 11.4% (⁹⁴⁄₈₂₈). Compared with patients without LM, those with LM had a higher proportion of unmethylated MGMT (76.6% vs. 64.6%, p = 0.021), larger tumor volumes (27.7 cm³ vs. 17.6 cm³, p < 0.001), and a higher proportion of midline tumors (22.3% vs. 10.8%, p = 0.001). Additionally, the distance between the tumor and the subventricular zone (SVZ) was shorter in LM patients (0 mm vs. 1.0 mm, p < 0.001).

Clinical and Imaging Characteristics of LM Patients

All 94 LM patients showed LM on brain MRI, and 72.4% were also detected with LM during spinal MRI. Among the eight patients who underwent CSF cytology, 87.5% were positive for LM. Overall survival was significantly shorter in LM patients compared to those without LM (12.2 months vs. 18.5 months, p < 0.001).

Risk Factors Affecting LM

Multivariate analysis showed that unmethylated MGMT (OR = 1.76, p = 0.008), shorter distance between the tumor and the SVZ (OR = 0.96, p = 0.005), and larger contrast-enhanced tumor volume (OR = 1.02, p < 0.001) were significantly associated with LM.

Survival Analysis and Prognosis Assessment

Kaplan-Meier survival curves indicated that patients with LM had significantly shorter survival times than those without LM (OS: 12.2 vs. 18.5 months, p < 0.001). Multivariate Cox regression analysis revealed that clinical prognosis was significantly influenced by various factors, including the presence of LM. The existence of LM was an independent adverse prognostic factor (HR = 1.47, p = 0.006).

Research Conclusions

This study demonstrates that the incidence of LM in IDH wild-type glioblastoma patients is relatively high (11.4%). Positive molecular and imaging factors such as unmethylated MGMT, shorter distances between the tumor and the SVZ, and larger tumor volumes are significantly associated with LM. Postoperative contrast-enhanced FLAIR imaging, as a highly sensitive diagnostic tool, can be reliably used for clinical LM diagnosis. The presence of LM results in poorer survival outcomes, suggesting that clinicians should pay close attention to the high incidence of LM and its associated factors, thereby enhancing awareness and clinical research on this relatively overlooked condition.

Research Highlights

1. High Incidence of LM: Through large-scale patient data analysis, this study reveals a relatively high incidence of LM in IDH wild-type glioblastoma.
2. Precise Image Diagnosis: Postoperative contrast-enhanced FLAIR imaging performs excellently in LM detection, providing higher lesion visibility.
3. Significant Prognostic Impact: The presence of LM is an independent adverse prognostic factor, emphasizing the importance of LM diagnosis and treatment.