Leptomeningeal metastases in glioma revisited: incidence and molecular predictors based on postcontrast fluid-attenuated inversion recovery imaging

Abstract

OBJECTIVE Leptomeningeal metastases (LMs) in glioma have been underestimated given their low incidence and the lack of reliable imaging. Authors of this study aimed to investigate the real-world incidence of LMs using cerebrospinal fluid (CSF)–sensitive imaging, namely postcontrast fluid-attenuated inversion recovery (FLAIR) imaging, and to analyze molecular predictors for LMs in the molecular era. METHODS A total of 1405 adult glioma (World Health Organization [WHO] grade 2–4) patients underwent postcontrast FLAIR imaging at initial diagnosis and during treatment monitoring between 2001 and 2021. Collected molecular data included isocitrate dehydrogenase (IDH) mutation, 1p/19q codeletion, H3 K27 alteration, and O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation status. LM diagnosis was performed with MRI including postcontrast FLAIR sequences. Logistic regression analysis for LM development was performed with molecular, clinical, and imaging data. Overall survival (OS) was compared between patients with and those without LM. RESULTS LM was identified in 228 patients (16.2%), 110 (7.8%) at the initial diagnosis and 118 (8.4%) at recurrence. Among the molecular diagnostics, IDH-wildtype (OR 3.14, p = 0.001) and MGMT promoter unmethylation (OR 1.43, p = 0.034) were independent predictors of LM. WHO grade 4 (OR 10.52, p < 0.001) and nonlobar location (OR 1.56, p = 0.048) were associated with LM at initial diagnosis, whereas IDH-wildtype (OR 5.04, p < 0.001) and H3 K27 alteration (OR 3.39, p = 0.003) were associated with LM at recurrence. Patients with LM had a worse median OS than those without LM (16.7 vs 32.0 months, p < 0.001, log-rank test), which was confirmed as an independent factor on multivariable Cox analysis (p = 0.004). CONCLUSIONS CSF-sensitive imaging aids the diagnosis of LM, demonstrating a high incidence of LM in adult gliomas. Furthermore, molecular markers are associated with LM development in glioma, and patients with aggressive molecular markers warrant imaging surveillance for LM.

The 2021 WHO Classification for Gliomas and Implications on Imaging Diagnosis: Part 2—Summary of Imaging Findings on Pediatric‐Type Diffuse High‐Grade Gliomas, Pediatric‐Type Diffuse Low‐Grade Gliomas, and Circumscribed Astrocytic Gliomas

“…A recent study from the international DIPG registry showed that the presence of ill‐defined signal infiltrating pontine fibers is the only imaging feature associated with histone mutation in DIPG 27 . The rate of leptomeningeal metastases is high in diffuse midline glioma, H3 K27‐altered; a large autopsy‐based study described a rate of 40%, 28 and we recently reported that a similar detection rate of 39.8% can be achieved by routine imaging including postcontrast FLAIR imaging 29 . Figure 4 shows representative cases of typical imaging features of diffuse midline glioma, H3 K27‐altered.…”

“…27 The rate of leptomeningeal metastases is high in diffuse midline glioma, H3 K27-altered; a large autopsy-based study described a rate of 40%, 28 and we recently reported that a similar detection rate of 39.8% can be achieved by routine imaging including postcontrast FLAIR imaging. 29 Figure 4 shows representative cases of typical imaging features of diffuse midline glioma, H3 K27-altered. Figure 5 shows a representative case with leptomeningeal metastases on follow-up imaging.…”

The 2021 WHO Classification for Gliomas and Implications on Imaging Diagnosis: Part 1—Key Points of the Fifth Edition and Summary of Imaging Findings on Adult‐Type Diffuse Gliomas

“…The recommended imaging protocol of adult gliomas includes 3D precontrast and postcontrast T1‐weighted imaging, 2D postcontrast T2‐weighted and precontrast fluid‐attenuation inversion recovery (FLAIR) imaging, and 2D diffusion‐weighted imaging 19 . Postcontrast FLAIR is not a routinely recommended sequence in glioma, but from our personal experience, we strongly believe that this sequence is useful in detection of leptomeningeal metastases 20 …”

“…19 Postcontrast FLAIR is not a routinely recommended sequence in glioma, but from our personal experience, we strongly believe that this sequence is useful in detection of leptomeningeal metastases. 20…”

The Riddle of the Sphinx: Progress in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

“…The RANO-BM standard mainly corresponds to brain metastases, and for most brain metastases, the distance between the 2 vertical cross paths can be measured, and brain metastases are very different from meningeal metastases in imaging performance. 101 , 102 Brain metastases are easy to diagnose in imaging, but LM lesions are not easily determined in imaging, which is currently a major challenge for imaging.…”