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

• Published in: Reports of practical oncology and radiotherapy Vol. 27; no. 5; pp. 759 - 767
• Main Authors: Salah, Samer, Naser, Walid, Jaber, Omar, Saleh, Yacob, Mustafa, Rawan, Abuhijlih, Ramiz, Abuhijla, Fawzi, Ismaeel, Taleb, Yaser, Sameer, Sultan, Iyad, Mustafa, Nour, Tbakhi, Abdelghani
• Format: Journal Article
• Language: English
• Published: Via Medica 31-10-2022
• Subjects: Research Paper
• ISSN: 1507-1367; 2083-4640
• DOI: 10.5603/RPOR.a2022.0084

BackgroundThere 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 methodsData 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. ResultsA 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. ConclusionMGMT-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.