# Prognostic impact of radiotherapy timing in WHO grade 2 and 3 meningiomas utilizing an integrated molecular-morphologic classification

## TL;DR

This study shows that combining molecular and morphological data improves prediction of meningioma outcomes and helps determine the best timing for radiotherapy.

## Contribution

The study introduces an integrated molecular-morphological score that enhances risk prediction for meningioma patients beyond traditional WHO classification.

## Key findings

- MF-malignant meningiomas had a 0% local failure-free survival after 5 years, while MF-benign had 77%.
- Copy Number Variations correlated significantly with local failure-free survival in patients receiving radiotherapy.
- The IntS model showed distinct survival disparities across risk categories, emphasizing the value of combined molecular and morphological data.

## Abstract

Meningiomas (MNGs) occur in different histopathological subtypes. The WHO grading system classifies a subset as grade 2 and 3, indicating a more aggressive course. Recent advances in risk stratification introduces an integrated molecular-morphological score (IntS), offering improved risk prediction over the traditional WHO classification. This study aims to evaluate the prognostic utility of IntS in the context of the timing of adjuvant radiotherapy (RT).

This retrospective study analyzed 55 patients with histologically diagnosed WHO grade 2 and 3 MNG treated with adjuvant RT. Molecular analyses using Illumina 450k Human BeadChip and Illumina 850k EPIC stratified patients into 3 risk groups (low, intermediate and high) using an integrated model that combines WHO grading, Copy Number Variations (CNVs), and Methylation Families (MF).

After 5 years a local failure-free survival (LFFS) rate of 0% in MF-malignant MNG contrasts with a LFFS rate of 77% and 58% in MF-benign and MF-intermediate MNG. A significant correlation between CNVs and LFFS was also observed in the adjuvant setting. The IntS model revealed distinct 5-year LFFS disparities across different risk categories, underscoring the impact of combined morphological and molecular characteristics on outcome.

The integration of DNA-methylation and CNV-profiles into the IntS unified risk score offer an enhanced prognostic differentiation of MNG patients. This approach shows a promising direction for guiding the optimal timing of adjuvant RT, offering a path toward more tailored treatment strategies for meningiomas.