GLIMMER: an interim subgroup analysis from an ongoing prospective study evaluating hyperspectral imaging for MGMT promoter methylation in gliomas

TL;DR

This study explores using hyperspectral imaging to quickly predict MGMT promoter methylation in gliomas during surgery, which could help guide treatment decisions.

Contribution

The study introduces GLIMMER, a novel optical scoring system using hyperspectral imaging to predict MGMT methylation status intraoperatively.

Findings

The GLIMMER score achieved an AUC of 0.95 with high sensitivity and specificity for MGMT methylation prediction.

In glioblastoma patients, the score showed 100% sensitivity and 75% specificity.

Patients with higher GLIMMER scores had significantly higher MGMT methylation rates.

Abstract

MGMT promoter methylation is of importance in glioma regarding prognosis and management. Non-methylated MGMT glioblastoma patients seem to benefit more from gross total resection. MGMT status is not ultra-rapidly available in the operating room. The presents study is the first aiming to evaluate whether the novel imaging technique intraoperative hyperspectral imaging (HSI) can predict MGMT promoter methylation status in glioma patients using a novel optical scoring system.

This was a prospective subgroup analysis of 25 glioma patients enrolled in a single-center observational study. Patients underwent in-vivo HSI (spectral range: 500–1000 nm) targeting non-contrast-enhancing tumor regions during resection. Two optical parameters—tissue water index (TWI) and organ hemoglobin index (OHI)—were extracted and combined into a novel three-point GLIMMER score. Primary endpoint was MGMT promoter methylation status determined by pyrosequencing. Diagnostic performance of the GLIMMER score was measured by AUC, sensitivity, and specificity. A subgroup analysis focused on IDH-wild-type glioblastoma (n = 16).

OHI ≤ 0.606 and TWI ≥ 0.501 were significantly associated with MGMT promoter methylation. The combined GLIMMER score achieved an AUC of 0.95 (95% CI, 0.87–1.00) with 94.7% sensitivity and 83.3% specificity. In the glioblastoma subgroup, the AUC was 0.97, with 100% sensitivity and 75% specificity. Patients scoring ≥ 1 point had significantly higher MGMT methylation (31.5%) than those scoring 0 points (7.9%; p < 0.001).

The GLIMMER score suggests potential ultra-rapid, non-invasive intraoperative estimation of MGMT promoter methylation with high diagnostic performance. These findings necessitate further validation with in-vivo HSI-guided biopsies to guide future personalized resection strategies in glioma patients.

German Clinical Trials Register (DRKS, Trial number: DRKS00036771, Registration date: 05.05.2025).

The online version contains supplementary material available at 10.1007/s11060-025-05340-2.

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