MGMT Promoter Methylation: Prognostication beyond Treatment Response
Keyoumars Ashkan, Asfand Baig Mirza, Christos Soumpasis, Christoforos Syrris, Dimitrios Kalaitzoglou, Chaitanya Sharma, Zachariah Joseph James, Abbas Khizar Khoja, Razna Ahmed, Amisha Vastani, James Bartram, Kazumi Chia, Omar Al‐Salihi, Angela Swampilai, Lucy Brazil, Ross C. Laxton, Zita Reisz, István Bódi, Andrew King, Richard Gullan, Francesco Vergani, Ranjeev Bhangoo, Safa Al‐Sarraj, José Pedro Lavrador
Abstract
MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.