The Impact of Surgery in IDH 1 Wild Type Glioblastoma in Relation With the MGMT Deregulation.

Francesco Marchi,Samantha Epistolio,Luca Mazzucchelli,Roberta Cerutti,Milo Frattini,Nora Sahnane,Jessica Barizzi,Michael Reinert,Debora Cipriani,Federico Mattia Stefanini,Fausto Sessa,Gianfranco Angelo Pesce,Sergio Balbi,Michele Cerati

doi:10.3389/fonc.2019.01569

Abstract

Object: The treatment of choice in glioblastoma (GBM) is the maximal surgical extent of resection (EOR) followed by adjuvant chemo-radiotherapy. Furthermore, methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with prolonged overall survival (OS) and progression free survival (PFS). The objective of the present study is correlate the biomolecular aspects in relation with EOR.Materials and methods: We analyzed a series of 116 patients with IDH-1 wild type GBM and different EOR (Gross Total Resection—GTR-, Partial Resection—PR- and Biopsy), treated with adjuvant chemo-radiotherapy. The MGMT status was analyzed in terms of promoter methylation and protein expression.Results: When GTR was possible, OS and PFS were significantly better compared to the other two groups (p = 0.001 and p = 0.035, respectively). MGMT methylation was significantly associated with better OS in the biopsy group (p = 0.022) and better OS and PFS in PR (p = 0.02 and p = 0.012, respectively), but not in the GTR group (p = 0.252 for OS, p = 0.256 for PFS) nor the PFS in the biopsy group (p = 0.259). MGMT protein expression levels do not show any association with OS and PFS, regardless of the type of surgery.Conclusions: Our study confirms the positive association of a safe maximal EOR with better OS and PFS, and indicates a positive prognostic value of MGMT methylation status only in case of the presence of residual tumor tissue. MGMT protein expression seems not to play a clinical role in relation with the type of surgery.

Highlights

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults [1]
The aim of this study is to assess the relation between extent of resection (EOR) and Methylguanine-DNA methyltransferase (MGMT) status by analyzing the clinical outcome (PFS and overall survival (OS)) of radio-chemotherapy treated IDH1 wild type GBM patients, in correlation with the type of surgery
Inclusion criteria consist of age >18 years, histological diagnosis of Isocitrate Dehydrogenase (IDH)-1 wild type GBM (WHO IV), therapy with TMZ according with the Stupp scheme (60 Gray radiotherapy and concomitant chemotherapy with TMZ, followed by six cycles of maintenance TMZ), death caused by GBM, tissue availability for biomolecular analyses

Summary

Introduction

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults [1]. Currently, safe optimal surgical resection followed by adjuvant radiotherapy and chemotherapy is considered as the standard treatment approach for patients with GBM [2,3,4]. Many studies have reported a positive correlation between the extent of resection (EOR) and the overall survival (OS) in patients with GBM, in particular for patients undergoing Gross Total Resection (GTR) with respect to whom receiving only a Subtotal Tumor Resection (STR) [5]. Even the propensity score matching (PSM) between the PR and biopsy groups, according with this study, did not show any significant difference in OS and PFS between the groups (p = 0.51 and 0.75, respectively). The hazard ratios for OS and PFS of PR compared with biopsy were 0.98 and 0.73, respectively; the difference was not statistically significant (p = 0.96 and 0.39, respectively).

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Conclusion