The O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide

The O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide

There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O -methylguanine-DNA methyltransferase ( ) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozolomide (IT), PFS f...

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Bibliographic Details
Published in:Reports of practical oncology and radiotherapy Vol. 27; no. 5; p. 759
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: Poland 2022
Subjects:
Ewing sarcoma
MGMT methylation
biomarkers
survival
prognosis
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Summary:There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O -methylguanine-DNA methyltransferase ( ) 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). Data of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE. 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. A total of 20 ES patients underwent promoter methylation testing, and were eligible for analysis. Five patients (25%) had methylated , 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 . unmethylated 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 . 8.6 months, p = 0.034. Median OS was superior but not statistically significant in the methylated group. -promoter methylation did not correlate with clinical activity or outcomes following the IT regimen for advanced ES. However, methylated predicted significantly superior PFS following initiation of the standard VDC-IE protocol.
ISSN:1507-1367