Abstract

Background: The association between contrast enhanced (CE) and non-contrast enhanced (NCE) tumor resection and survival in patients with glioblastoma in relation to molecular subtypes is poorly understood. The aim of this study was to assess the association between CE and NCE tumor resection and survival in light of MGMT promoter methylation in newly diagnosed IDH-wildtype glioblastoma.Materials and methods: Patients with newly diagnosed IDH-wildtype glioblastoma who underwent surgery were eligible. CE and NCE tumor volumes were assessed on pre- and post-operative MRI scans and extent of resection was calculated. The association between CE and NCE tumor resection and survival was evaluated using multivariable Cox proportional hazards models and Kaplan Meier estimates.Results: Three hundred and twenty-six patients were included: 177 (54.3%) with and 149 (45.7%) without MGMT methylation. Multivariable Cox proportional hazards models stratified for MGMT methylation identified age ≤ 65y (HR 0.63; 95% CI, 0.49–0.81; p < 0.0001), chemoradiation (HR 0.13; 95% CI, 0.09–0.19; p < 0.0001), maximal CE tumor resection (HR 0.58; 95% CI, 0.39–0.87; p = 0.009), ≥ 30% NCE tumor resection (HR 0.71; 95% CI, 0.53–0.93; p = 0.014), and minimal residual CE tumor volume (HR 0.64; 95% CI, 0.46–0.88 p = 0.007) as being associated with longer overall survival. Kaplan Meier estimates showed that extensive surgery was more beneficial for patients with MGMT methylated glioblastoma.Conclusions: This study shows an association between maximal CE tumor resection, ≥30% NCE tumor resection, minimal residual CE tumor volume, and longer overall survival in patients with newly diagnosed IDH wildtype glioblastoma. Intraoperative imaging and stimulation mapping may be used to pursue safe and maximal resection. In future research, the safety aspect of maximizing tumor resection needs to be addressed.

Highlights

  • Patients with glioblastoma have a poor prognosis with a median overall survival of 10–15 months, despite safe and maximal surgical resection followed by chemo- and radiotherapy [1]

  • 326 isocitrate dehydrogenase (IDH)-wildtype glioblastoma were included in our analysis: 177 (54.3%) with and 149 (45.7%) without methylguanine methyltransferase (MGMT) promoter methylation

  • Median overall survival and progression-free survival (PFS) was 309 days and 174 days, respectively

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Summary

Introduction

Patients with glioblastoma have a poor prognosis with a median overall survival of 10–15 months, despite safe and maximal surgical resection followed by chemo- and radiotherapy [1] This prognosis varies based on known factors such as age, KPS, extent of resection, isocitrate dehydrogenase (IDH) mutation status, and methylguanine methyltransferase (MGMT) promoter methylation status [2, 3]. Glioblastoma is known to infiltrate far beyond the margins of CE as seen on MRI, into the surrounding non-contrast enhanced (NCE) edematous T2-weighted or FLAIR abnormality area [4] This raises the question whether maximal CE tumor resection should be extended beyond CE, into NCE area, to improve survival [5]. The aim of this study was to assess the association between CE and NCE tumor resection and survival in light of MGMT promoter methylation in newly diagnosed IDH-wildtype glioblastoma

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