MGMT promoter methylation modulates the effect of residual tumor on survival after re-resection of recurrent glioblastoma
Surgical re-resection for recurrent IDH-wildtype glioblastoma remains controversial, and no molecular biomarkers currently inform on tailoring the extent of cytoreduction and hence onco-functional balance at recurrence. On the other hand, while the prognostic relevance of O6-methylguanine-DNA-methyl...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 February 2026
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| In: |
Acta Neuropathologica Communications
Year: 2026, Volume: 14, Pages: 1-12 |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-026-02234-w |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s40478-026-02234-w
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| Author Notes: | Obada T. Alhalabi, Lukas Klein, Kirill Mironov, Lukas Beyl, Tobias Kessler, Christine Jungk, Philipp Sievers, Felix Sahm, Martin Bendszus, Wolfgang Wick, Bogdana Suchorska, Sandro M. Krieg and Sebastian Ille |
| Summary: | Surgical re-resection for recurrent IDH-wildtype glioblastoma remains controversial, and no molecular biomarkers currently inform on tailoring the extent of cytoreduction and hence onco-functional balance at recurrence. On the other hand, while the prognostic relevance of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is established in glioblastoma. Its role in surgical decision-making at recurrence remains unclear. We analyzed a cohort of 153 patients who underwent re-resection for IDH-wildtype recurrent glioblastoma (WHO classification 2021) between 2015 and 2024. Volumetric analysis of contrast-enhancing (CE) tumor on pre- and early postoperative MRI was performed. Patients were stratified by MGMT promoter methylation status and residual tumor volume (RTV): 0 ml, < 1 ml, > 1 ml. Functional outcomes up to one year after surgery were longitudinally assessed using the National Institutes of Health Stroke Scale (NIHSS). There was no significant difference in RTV between MGMT-methylated (n = 58, 38%) and unmethylated patients (p > 0.999). The benefit from complete or near-complete resection was more pronounced in MGMT-unmethylated tumors, with a median postoperative survival of 288 days for 0 to 1 ml RTV versus 190 days > 1 ml (p = 0.024; difference = 98 days), compared to MGMT-methylated tumors with a median survival of 411 days versus 378 days (p = 0.043; difference = 33 days). MGMT-unmethylated patients with 0 ml RTV showed significantly higher KPS values six weeks postoperatively (p < 0.05) compared to higher RTVs. Postoperative deficits were comparable across groups. These findings identify MGMT promoter methylation as a clinically actionable molecular modifier of the oncological benefit of cytoreduction and support MGMT-stratified, precision neurosurgical strategies for recurrent glioblastoma, especially around functionally eloquent tumors. - SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-026-02234-w. |
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| Item Description: | Gesehen am 08.06.2026 |
| Physical Description: | Online Resource |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-026-02234-w |