Does positive MGMT methylation outbalance the limitation of subtotal resection in glioblastoma IDH-wildtype patients?

Abstract

Background: The impact on survival of complete resection (CR) in patients with malignant glioma and MGMT promoter methylation on adjuvant therapy strategies has been proven in the past. However, it is not known whether a MGMT promoter methylation can compensate a subtotal resection. Therefore, we analyzed the progress of postoperative residual tumor tissue depending on the molecular tumor status. Methods: We included all glioblastoma, IDH-wildtype (WHO grade IV) patients with postoperative residual tumor tissue, who were treated at our neurooncological department between 2010 and 2018. Correlation of molecular patterns with clinical data and survival times was performed. The results were compared to patients following CR. Results: 267 patients with glioblastoma, IDH-wildtype (WHO grade IV) received surgery of whom 81 patients with residual tumor were included in the analysis. MGMT promoter was methylated in 31 patients (38.27%). Median OS and PFS were significantly increased in patients with methylated MGMT promoter (mOS: 16 M vs. 13 M, p = 0.009; mPFS: 13 M vs. 5 M, p = 0.003). In comparison to survival of patients following CR, OS was decreased in patients with residual tumor regardless MGMT methylation. Conclusion: Our data confirm impact of MGMT promoter methylation in patients with glioblastoma, IDH-wildtype on OS and PFS. However, in comparison to patients after CR, a methylated MGMT promoter cannot compensate the disadvantage due to residual tumor volume. In terms of personalized medicine and quality of life as major goal in oncology, neuro-oncologists have to thoroughly discuss advantages and disadvantages of residual tumor volume versus possible neurological deficits in CR.