The O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide

التفاصيل البيبلوغرافية
العنوان: The O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide
المؤلفون: Salah, Samer, Naser, Walid, Jaber, Omar, Saleh, Yacob, Mustafa, Rawan, Abuhijlih, Ramiz, Abuhijla, Fawzi, Ismaeel, Taleb, Yaser, Sameer, Sultan, Iyad, Mustafa, Nour, Tbakhi, Abdelghani
المصدر: Reports of Practical Oncology and Radiotherapy; Vol 27, No 5 (2022); 759-767
بيانات النشر: Via Medica
سنة النشر: 2022
المجموعة: Via Medica Journals
مصطلحات موضوعية: Ewing sarcoma, biomarkers, MGMT methylation, prognosis, survival
الوصف: Background: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O6-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.
نوع الوثيقة: other/unknown material
وصف الملف: application/pdf
اللغة: English
العلاقة: https://journals.viamedica.pl/rpor/article/view/RPOR.a2022.0084Test
DOI: 10.5603/RPOR.a2022.0084
الإتاحة: https://doi.org/10.5603/RPOR.a2022.0084Test
https://journals.viamedica.pl/rpor/article/view/RPOR.a2022.0084Test
حقوق: Completion of the online submission form electronically (the Author's Statement) is tantamount to automatic transfer of the copyright for publishing and distribution of the submitted material (in all current and future forms and fields of exploitation) to the Copyright Owner, i.e. Greater Poland Cancer Centre (Poznan, Poland), on condition that these materials are accepted for publication. The authors agree not to publish any data or figures presented in their work in any place or in any language without the prior written consent of the Publisher.
رقم الانضمام: edsbas.D41762C
قاعدة البيانات: BASE