# Proliferation-Diffusion Modeling in Glioblastoma: Impact of Supramaximal Resection on Survival

## TL;DR

This study shows that moderately diffuse glioblastoma tumors with methylated MGMT benefit most from aggressive surgery, improving survival outcomes.

## Contribution

First study to integrate RANO resection criteria with tumor invasiveness profiles using the proliferation–diffusion model in GBM.

## Key findings

- MGMT methylation significantly improves survival in moderately diffuse tumors.
- SUPR provides survival benefits specifically for moderately diffuse GBM with methylated MGMT.
- MGMT status is an independent predictor of overall survival in GBM patients.

## Abstract

Glioblastoma (GBM) aggressive growth, early recurrence, and poor prognosis highlight the need for innovative therapeutic strategies. This single-center retrospective study is aimed to evaluate the role of the tumor invasiveness profile, assessed through the ρ/D ratio, in a homogeneous cohort of patients with newly diagnosed GBM-2021 WHO that underwent supramaximal resection (SUPR) according to RANO criteria, and to analyze its impact on survival outcomes. This is the first study that integrates the new RANO classification system for the extent of resection (EOR) in GBM surgery and correlates it with the tumor invasiveness profile. Using the proliferation–diffusion model to classify tumors, we identified moderately diffuse tumors with methylated MGMT status as a subgroup with significant survival benefits from SUPR.

Purpose: To evaluate the role of tumor invasiveness profile in a homogeneous cohort of patients with newly diagnosed GBM (2021 WHO) that underwent SUPR by the RANO criteria, and to analyze its impact on survival outcomes. Methods: Patients with newly diagnosed, histologically confirmed glial tumors featuring contrast-enhancing lesions, who underwent surgery at our institution between January 2007 and January 2024, were retrospectively reviewed. Preoperative total tumor volume (T-TV), contrast-enhancing (CE), and infiltrative FLAIR tumor volume (FLAIR-TV) were calculated in cubic centimeters (cc) via manual segmentation. A neuronavigation system was utilized for surgery and lesions were molecularly evaluated following the 2021 WHO CNS tumor classification. Therefore, all patients were classified into extent of resection categories by the 2022 RANO-Resect classification. The tumor invasiveness profile was assessed using the proliferation/diffusion (ρ/D) ratio, calculated following Swanson’s method. A statistical analysis was finally performed. Results: Between 2007 and 2024, 410 adult patients with newly diagnosed gliomas were treated at our institution. Methylation of the MGMT promoter was statistically significant (HR = 0.43, 95% CI: 0.20–0.94, p = 0.035), indicating that methylation has a protective effect on survival. In multivariate analysis, only MGMT status was confirmed to be an independent predictor of overall survival (OS). MGMT methylation was significantly associated with improved progression-free survival (PFS) in moderately diffuse tumors (HR = 0.18, 95% CI: 0.03–0.95, p = 0.044). Conclusions: Using the proliferation–diffusion model to classify tumors, we identified moderately diffuse tumors with methylated MGMT status as a subgroup with significant survival benefits from SUPR.