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The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide
BACKGROUND: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozol...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Via Medica
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746634/ https://www.ncbi.nlm.nih.gov/pubmed/36523794 http://dx.doi.org/10.5603/RPOR.a2022.0084 |
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author | Salah, Samer Naser, Walid Jaber, Omar Saleh, Yacob Mustafa, Rawan Abuhijlih, Ramiz Abuhijla, Fawzi Ismaeel, Taleb Yaser, Sameer Sultan, Iyad Mustafa, Nour Tbakhi, Abdelghani |
author_facet | Salah, Samer Naser, Walid Jaber, Omar Saleh, Yacob Mustafa, Rawan Abuhijlih, Ramiz Abuhijla, Fawzi Ismaeel, Taleb Yaser, Sameer Sultan, Iyad Mustafa, Nour Tbakhi, Abdelghani |
author_sort | Salah, Samer |
collection | PubMed |
description | BACKGROUND: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozolomide (IT), PFS following initiation of vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), and overall survival (OS). MATERIALS AND METHODS: Data of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE. MGMT promoter methylation was assessed on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using methylation sensitive restriction enzyme-quantitative PCR (MSRE-qPCR). Survival was estimated by the Kaplan-Meier method. RESULTS: A total of 20 ES patients underwent MGMT promoter methylation testing, and were eligible for analysis. Five patients (25%) had methylated MGMT, whereas the remaining (15; 75%) had unmethylated promoter. Five (25%) had objective response to IT, with no observed difference by promoter methylation (p = 0.76). Median PFS from initiation of IT for methylated vs. unmethylated MGMT patients was 4.9 and 1.2 months, respectively, p = 0.69. Median PFS from date of initiation of VDC-IE was significantly superior in the methylated group; 27.8 vs. 8.6 months, p = 0.034. Median OS was superior but not statistically significant in the methylated group. CONCLUSION: MGMT-promoter methylation did not correlate with clinical activity or outcomes following the IT regimen for advanced ES. However, methylated MGMT predicted significantly superior PFS following initiation of the standard VDC-IE protocol. |
format | Online Article Text |
id | pubmed-9746634 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Via Medica |
record_format | MEDLINE/PubMed |
spelling | pubmed-97466342022-12-14 The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide Salah, Samer Naser, Walid Jaber, Omar Saleh, Yacob Mustafa, Rawan Abuhijlih, Ramiz Abuhijla, Fawzi Ismaeel, Taleb Yaser, Sameer Sultan, Iyad Mustafa, Nour Tbakhi, Abdelghani Rep Pract Oncol Radiother Research Paper BACKGROUND: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozolomide (IT), PFS following initiation of vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), and overall survival (OS). MATERIALS AND METHODS: Data of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE. MGMT promoter methylation was assessed on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using methylation sensitive restriction enzyme-quantitative PCR (MSRE-qPCR). Survival was estimated by the Kaplan-Meier method. RESULTS: A total of 20 ES patients underwent MGMT promoter methylation testing, and were eligible for analysis. Five patients (25%) had methylated MGMT, whereas the remaining (15; 75%) had unmethylated promoter. Five (25%) had objective response to IT, with no observed difference by promoter methylation (p = 0.76). Median PFS from initiation of IT for methylated vs. unmethylated MGMT patients was 4.9 and 1.2 months, respectively, p = 0.69. Median PFS from date of initiation of VDC-IE was significantly superior in the methylated group; 27.8 vs. 8.6 months, p = 0.034. Median OS was superior but not statistically significant in the methylated group. CONCLUSION: MGMT-promoter methylation did not correlate with clinical activity or outcomes following the IT regimen for advanced ES. However, methylated MGMT predicted significantly superior PFS following initiation of the standard VDC-IE protocol. Via Medica 2022-10-31 /pmc/articles/PMC9746634/ /pubmed/36523794 http://dx.doi.org/10.5603/RPOR.a2022.0084 Text en © 2022 Greater Poland Cancer Centre https://creativecommons.org/licenses/by-nc-nd/4.0/This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially |
spellingShingle | Research Paper Salah, Samer Naser, Walid Jaber, Omar Saleh, Yacob Mustafa, Rawan Abuhijlih, Ramiz Abuhijla, Fawzi Ismaeel, Taleb Yaser, Sameer Sultan, Iyad Mustafa, Nour Tbakhi, Abdelghani The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide |
title | The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide |
title_full | The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide |
title_fullStr | The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide |
title_full_unstemmed | The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide |
title_short | The O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide |
title_sort | o(6)-methylguanine-dna methyltransferase (mgmt) promoter methylation status and clinical outcomes of ewing sarcoma patients treated with irinotecan and temozolomide |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746634/ https://www.ncbi.nlm.nih.gov/pubmed/36523794 http://dx.doi.org/10.5603/RPOR.a2022.0084 |
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