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MGMT Promoter Methylation: Prognostication beyond Treatment Response

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...

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Autores principales: Ashkan, Keyoumars, Baig Mirza, Asfand, Soumpasis, Christos, Syrris, Christoforos, Kalaitzoglou, Dimitrios, Sharma, Chaitanya, James, Zachariah Joseph, Khoja, Abbas Khizar, Ahmed, Razna, Vastani, Amisha, Bartram, James, Chia, Kazumi, Al-Salihi, Omar, Swampilai, Angela, Brazil, Lucy, Laxton, Ross, Reisz, Zita, Bodi, Istvan, King, Andrew, Gullan, Richard, Vergani, Francesco, Bhangoo, Ranjeev, Al-Sarraj, Safa, Lavrador, Jose Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302387/
https://www.ncbi.nlm.nih.gov/pubmed/37373988
http://dx.doi.org/10.3390/jpm13060999
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author Ashkan, Keyoumars
Baig Mirza, Asfand
Soumpasis, Christos
Syrris, Christoforos
Kalaitzoglou, Dimitrios
Sharma, Chaitanya
James, Zachariah Joseph
Khoja, Abbas Khizar
Ahmed, Razna
Vastani, Amisha
Bartram, James
Chia, Kazumi
Al-Salihi, Omar
Swampilai, Angela
Brazil, Lucy
Laxton, Ross
Reisz, Zita
Bodi, Istvan
King, Andrew
Gullan, Richard
Vergani, Francesco
Bhangoo, Ranjeev
Al-Sarraj, Safa
Lavrador, Jose Pedro
author_facet Ashkan, Keyoumars
Baig Mirza, Asfand
Soumpasis, Christos
Syrris, Christoforos
Kalaitzoglou, Dimitrios
Sharma, Chaitanya
James, Zachariah Joseph
Khoja, Abbas Khizar
Ahmed, Razna
Vastani, Amisha
Bartram, James
Chia, Kazumi
Al-Salihi, Omar
Swampilai, Angela
Brazil, Lucy
Laxton, Ross
Reisz, Zita
Bodi, Istvan
King, Andrew
Gullan, Richard
Vergani, Francesco
Bhangoo, Ranjeev
Al-Sarraj, Safa
Lavrador, Jose Pedro
author_sort Ashkan, Keyoumars
collection PubMed
description 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.
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spelling pubmed-103023872023-06-29 MGMT Promoter Methylation: Prognostication beyond Treatment Response Ashkan, Keyoumars Baig Mirza, Asfand Soumpasis, Christos Syrris, Christoforos Kalaitzoglou, Dimitrios Sharma, Chaitanya James, Zachariah Joseph Khoja, Abbas Khizar Ahmed, Razna Vastani, Amisha Bartram, James Chia, Kazumi Al-Salihi, Omar Swampilai, Angela Brazil, Lucy Laxton, Ross Reisz, Zita Bodi, Istvan King, Andrew Gullan, Richard Vergani, Francesco Bhangoo, Ranjeev Al-Sarraj, Safa Lavrador, Jose Pedro J Pers Med Article 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. MDPI 2023-06-14 /pmc/articles/PMC10302387/ /pubmed/37373988 http://dx.doi.org/10.3390/jpm13060999 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ashkan, Keyoumars
Baig Mirza, Asfand
Soumpasis, Christos
Syrris, Christoforos
Kalaitzoglou, Dimitrios
Sharma, Chaitanya
James, Zachariah Joseph
Khoja, Abbas Khizar
Ahmed, Razna
Vastani, Amisha
Bartram, James
Chia, Kazumi
Al-Salihi, Omar
Swampilai, Angela
Brazil, Lucy
Laxton, Ross
Reisz, Zita
Bodi, Istvan
King, Andrew
Gullan, Richard
Vergani, Francesco
Bhangoo, Ranjeev
Al-Sarraj, Safa
Lavrador, Jose Pedro
MGMT Promoter Methylation: Prognostication beyond Treatment Response
title MGMT Promoter Methylation: Prognostication beyond Treatment Response
title_full MGMT Promoter Methylation: Prognostication beyond Treatment Response
title_fullStr MGMT Promoter Methylation: Prognostication beyond Treatment Response
title_full_unstemmed MGMT Promoter Methylation: Prognostication beyond Treatment Response
title_short MGMT Promoter Methylation: Prognostication beyond Treatment Response
title_sort mgmt promoter methylation: prognostication beyond treatment response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302387/
https://www.ncbi.nlm.nih.gov/pubmed/37373988
http://dx.doi.org/10.3390/jpm13060999
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