TY - JOUR
T1 - MGMT methylation and its prognostic significance in inoperable IDH-wildtype glioblastoma
T2 - the MGMT-GBM study
AU - Ghimire, Prajwal
AU - Kamaludin, Ahmad
AU - Palau, Berta F
AU - Lavrador, Jose P
AU - Gullan, Richard
AU - Vergani, Francesco
AU - Bhangoo, Ranjeev
AU - Ashkan, Keyoumars
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/10/5
Y1 - 2024/10/5
N2 - INTRODUCTION: The methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis in IDH-wildtype(IDH-w) glioblastoma. We aim to study the impact of its methylation in overall survival of the unresectable IDH-w glioblastoma undergoing biopsy and systemic treatment.METHODS: We collected six-year retrospective (2017-2023) data at a quaternary neurosurgery center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology multidisciplinary team meeting (MDT) documentation. Patients were grouped into categories according to different types of treatment received after biopsy (no treatment, chemotherapy (CT), radiotherapy (RT), chemoradiotherapy (CRT), chemoradiotherapy with adjuvant temozolomide (CRT with adjuvant TMZ), EORTC-NCIC protocol followed by second line treatment) and according to methylation status (unmethylated (< 5%), borderline methylated (5-15%) and strongly methylated (> 15%)). Survival analysis was performed.RESULTS: 166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 70 (49.3%) patients had unmethylated MGMT status (< 5%), 29 (20.4%) patients had borderline methylated MGMT status (5-15%) and 43 (30.2%) patients had methylated MGMT status (> 15%). 36 (25.3%) patients did not receive any treatment post biopsy, 13 (9.1%) received CT only, 27 (19%) RT only, 12 (8.4%) CRT, 33 (23.2%) CRT with adjuvant TMZ, whereas 21 (14.7%) received EORTC-NCIC protocol along with second line treatment. In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment methylated groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups.CONCLUSION: Methylated MGMT status are predictors for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment regardless of the treatment modality.
AB - INTRODUCTION: The methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis in IDH-wildtype(IDH-w) glioblastoma. We aim to study the impact of its methylation in overall survival of the unresectable IDH-w glioblastoma undergoing biopsy and systemic treatment.METHODS: We collected six-year retrospective (2017-2023) data at a quaternary neurosurgery center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology multidisciplinary team meeting (MDT) documentation. Patients were grouped into categories according to different types of treatment received after biopsy (no treatment, chemotherapy (CT), radiotherapy (RT), chemoradiotherapy (CRT), chemoradiotherapy with adjuvant temozolomide (CRT with adjuvant TMZ), EORTC-NCIC protocol followed by second line treatment) and according to methylation status (unmethylated (< 5%), borderline methylated (5-15%) and strongly methylated (> 15%)). Survival analysis was performed.RESULTS: 166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 70 (49.3%) patients had unmethylated MGMT status (< 5%), 29 (20.4%) patients had borderline methylated MGMT status (5-15%) and 43 (30.2%) patients had methylated MGMT status (> 15%). 36 (25.3%) patients did not receive any treatment post biopsy, 13 (9.1%) received CT only, 27 (19%) RT only, 12 (8.4%) CRT, 33 (23.2%) CRT with adjuvant TMZ, whereas 21 (14.7%) received EORTC-NCIC protocol along with second line treatment. In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment methylated groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups.CONCLUSION: Methylated MGMT status are predictors for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment regardless of the treatment modality.
KW - Humans
KW - Glioblastoma/genetics
KW - Female
KW - Middle Aged
KW - Male
KW - Brain Neoplasms/genetics
KW - Tumor Suppressor Proteins/genetics
KW - DNA Repair Enzymes/genetics
KW - DNA Modification Methylases/genetics
KW - Aged
KW - Isocitrate Dehydrogenase/genetics
KW - Retrospective Studies
KW - Prognosis
KW - DNA Methylation/genetics
KW - Adult
UR - http://www.scopus.com/inward/record.url?scp=85205763399&partnerID=8YFLogxK
U2 - 10.1007/s00701-024-06300-x
DO - 10.1007/s00701-024-06300-x
M3 - Article
C2 - 39367282
SN - 0001-6268
VL - 166
JO - Acta Neurochirurgica
JF - Acta Neurochirurgica
IS - 1
M1 - 394
ER -
