Exome sequencing grades meningiomas and links surgery and radiotherapy to recurrence risk

Researchers have developed a simplified molecular grading system for meningiomas based on whole-exome sequencing, and used it to explore how two standard treatments relate to the risk of the tumor coming back. The retrospective study analyzed 456 patients who underwent surgical resection of intracranial meningiomas between 1999 and 2024, applying an exome-sequencing-based molecular grading (MG) scheme and then examining the associations of gross total resection (GTR) and postoperative adjuvant radiotherapy (RT) with recurrence-free survival (RFS) within each molecular group using propensity score–matched analyses.

The system sorts tumors into three categories using a small set of genomic features. Molecular grade A is defined by the presence of an NF2 mutation or loss of chromosome 22q together with the absence of high-risk molecular alterations. Molecular grade B is defined by the absence of both the NF2 mutation/22q loss and any high-risk alterations. Molecular grade C is defined by the presence of high-risk molecular alterations. The authors positioned this approach against existing molecular classifications of meningiomas, which they note improve biological and prognostic stratification but can be complex enough to hinder routine implementation, and whose treatment implications remain unclear.

Recurrence-free survival differed significantly across the three molecular grades, both in the entire cohort and in the clinically important subset of patients whose tumors were classified as WHO grade 1 meningiomas. All pairwise comparisons between grades A, B, and C reached statistical significance with false discovery rate–adjusted p values below 0.05.

The treatment associations varied by molecular subgroup. Gross total resection was associated with longer recurrence-free survival in the matched molecular grade B and grade C cohorts, with both comparisons yielding FDR-adjusted p values below 0.01. In molecular grade A, however, no statistically significant association was observed between the extent of resection and recurrence-free survival. Because the analysis was propensity score–matched within each molecular grade, the comparisons were made between patients with similar baseline characteristics, though the retrospective design still limits causal interpretation.

Adjuvant radiotherapy showed a more restricted pattern. In exploratory analyses, postoperative adjuvant RT was associated with longer recurrence-free survival in the matched molecular grade B cohort, with an FDR-adjusted p value of 0.005. By contrast, the analyses in molecular grades A and C were inconclusive, meaning the data did not support a clear conclusion about radiotherapy’s association with recurrence in those subgroups. The authors describe these radiotherapy findings as exploratory rather than definitive.

The study’s overall conclusion is that this simplified whole-exome-sequencing-based grading system stratified recurrence-free survival and enabled exploratory evaluation of treatment-associated outcomes within molecular subgroups. The work was published as an open access research article in Acta Neuropathologica Communications on 27 October 2026, and was shared early as a peer-reviewed, accepted, citable version subject to further edits before the final Version of Record.

Subject of Research: A whole-exome sequencing-based molecular grading system for meningiomas and its associations with surgical resection, adjuvant radiotherapy, and recurrence-free survival.

Article Title: Prognostic associations of surgical resection and adjuvant radiotherapy in meningioma defined by an exome–sequencing–based grading

Article References: Sakai, Y., Miyawaki, S., Komura, D., Hirano, Y., Umekawa, M., Teranishi, Y., Hongo, H., Ogawa, S., Tsuchiya, T., Sato, D., Hirata, S., Shinya, Y., Hasegawa, H., Ono, H., Katoh, H., Ishikawa, S., Kudo, N., Ikemura, M., Ushiku, T., & Saito, N. (2026). Prognostic associations of surgical resection and adjuvant radiotherapy in meningioma defined by an exome–sequencing–based grading. Acta Neuropathologica Communications. https://doi.org/10.1186/s40478-026-02462-0

Image Credits: AI Generated

DOI: 10.1186/s40478-026-02462-0

Keywords: meningioma, whole-exome sequencing, molecular grading, recurrence-free survival, gross total resection, adjuvant radiotherapy, NF2 mutation, 22q loss, WHO grade 1, propensity score matching, prognosis, neurosurgery