Understanding the difference in symptoms and outcomes between glioblastoma patients diagnosed based on histological or molecular criteria: a retrospective cohort analysis from the Histo-Mol GBM collaborative

Robinson, S.D. orcid.org/0000-0003-0623-4636, Kingdon, S. orcid.org/0000-0002-6582-9632, Williams, S.T. orcid.org/0000-0002-5843-0295 et al. (4 more authors) (2026) Understanding the difference in symptoms and outcomes between glioblastoma patients diagnosed based on histological or molecular criteria: a retrospective cohort analysis from the Histo-Mol GBM collaborative. Journal of Neuro-Oncology, 176 (2). 157. ISSN: 0167-594X

Abstract

PURPOSE: Since the 2021 World Health Organisation (WHO) classification, glioblastoma could be diagnosed based on classical histological features (hGBM) or molecular criteria (mGBM). However, prior studies included patients who required reclassification as a mGBM, potentially biasing survival analyses. The Histo-Mol GBM collaborative performed an international multicentre retrospective real-world cohort study of glioblastoma patients diagnosed according to WHO CNS 5.

METHODS: We identified consecutive patients diagnosed in 2021 with IDH wildtype glioblastoma according to WHO CNS 5. Clinicopathological, treatment, and survival data were collected and compared between mGBM and hGBM.

RESULTS: 1828 patients diagnosed with glioblastoma were included. 75 mGBM patients (8.4% of tested patients) were identified, with no difference in age (median 61 vs 64, p = 0.057), gender (p = 0.937), or proportion with performance status 0–1 (82.7% vs 68.3%, p = 0.052) compared to hGBM. mGBM patients had an extended interval from MRI to surgery (median 23 vs 14 days, p < 0.001) and more frequently underwent biopsy (69.3% vs 30.3%, p < 0.001), but equivalent proportions received oncological treatment (80.0% vs 78.7%, p = 0.784). Overall survival (OS) from surgery was not different (p = 0.063). However, OS from initial MRI, stratified by surgical extent, demonstrated improved OS for mGBM patients (hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.43–0.73). Propensity score matching identified improved survival following resection (HR 0.48, 95% CI: 0.24–0.95; median OS: 26.0 versus 14.0 months, p = 0.031) but not biopsy (HR 1.10, 95% CI: 0.71–1.72).

CONCLUSION: In this large real-world cohort, mGBMs had longer OS than hGBMs following resection with implications for prognostication and clinical decision making.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-025-05364-8.

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Item Type:	Article
Authors/Creators:	Robinson, S.D. https://orcid.org/0000-0003-0623-4636 Kingdon, S. https://orcid.org/0000-0002-6582-9632 Williams, S.T. https://orcid.org/0000-0002-5843-0295 Hill, C.S. https://orcid.org/0000-0002-4488-4034 Williams, M. https://orcid.org/0000-0001-7096-0718 Chandy, E. https://orcid.org/0000-0002-6117-8692 Critchley, G. https://orcid.org/0009-0008-2628-8176
Copyright, Publisher and Additional Information:	© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Classification; Glioblastoma; Histology; Molecular glioblastoma; Real-world evidence; Survival
Dates:	Submitted: 18 August 2025 Accepted: 1 December 2025 Published (online): 8 January 2026 Published: 8 January 2026
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Date Deposited:	27 Jan 2026 12:26
Last Modified:	27 Jan 2026 12:26
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1007/s11060-025-05364-8
Related URLs:	PubMed URL
Sustainable Development Goals:
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:236859

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Understanding the difference in symptoms and outcomes between glioblastoma patients diagnosed based on histological or molecular criteria: a retrospective cohort analysis from the Histo-Mol GBM collaborative

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