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接受甲基化 O(6)-甲基鸟嘌呤-DNA 甲基转移酶脑胶质瘤放化疗的患者可能从适度剂量递增放疗中获益。

Patients Affected by Unmethylated O(6)-Methylguanine-DNA Methyltransferase Glioblastoma Undergoing Radiochemotherapy May Benefit from Moderately Dose-Escalated Radiotherapy.

机构信息

Sbarro Health Research Organization, Temple University, Philadelphia, PA, USA.

Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy.

出版信息

Biomed Res Int. 2017;2017:9461402. doi: 10.1155/2017/9461402. Epub 2017 Oct 12.

Abstract

PURPOSE

To compare the therapeutic results of two radiotherapy (RT) dose schedules in combined temozolomide- (TMZ-) RT treatment in newly diagnosed glioblastoma (GB), according to the O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status.

MATERIAL AND METHOD

Patients received either standard (60 Gy) or moderately escalated dose (70 Gy) radiotherapy (RT) with concomitant and adjuvant TMZ between June 2006 and October 2013. We retrospectively evaluated the therapeutic effectiveness of RT schedules in terms of Overall Survival (OS) and Progression-Disease Free Survival (PDFS) analyzing the MGMT methylation status.

RESULTS

One hundred and seventeen patients were selected for the present analysis. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the escalated schedule (HDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in unmethylated-MGMT GB patients, HDRT-TMZ and SDRT-TMZ groups had different median OS ( = 0,01) and PDFS ( = 0,007), that is, 8 months and 5 months for the SDRT-TMZ group and 14 months and 9 months for the HDRT-TMZ group, respectively. No difference in survival outcomes was found in methylated MGMT patients according to the two RT schedules ( = 0,12).

CONCLUSIONS

In our experience, unmethylated-MGMT GB patients benefited from a moderately escalated dose of RT plus TMZ.

摘要

目的

根据 O(6)-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 甲基化状态,比较替莫唑胺 (TMZ) 联合放化疗新诊断胶质母细胞瘤 (GB) 中两种放疗 (RT) 剂量方案的治疗结果。

材料和方法

患者于 2006 年 6 月至 2013 年 10 月接受标准 (60Gy) 或适度递增剂量 (70Gy) 放疗 (RT) 联合替莫唑胺同期和辅助治疗。我们通过分析 MGMT 甲基化状态,回顾性评估了两种 RT 方案在总生存期 (OS) 和无进展疾病生存 (PDFS) 方面的治疗效果。

结果

本研究共纳入 117 例患者。其中 72 例患者接受标准 RT-TMZ 方案 (SDRT-TMZ),45 例患者接受递增剂量 RT-TMZ 方案 (HDRT-TMZ)。根据 MGMT 启动子甲基化状态分析显示,在未甲基化-MGMT 的 GB 患者中,HDRT-TMZ 和 SDRT-TMZ 组的中位 OS ( = 0.01) 和 PDFS ( = 0.007) 不同,SDRT-TMZ 组为 8 个月,5 个月,HDRT-TMZ 组为 14 个月和 9 个月。根据两种 RT 方案,甲基化 MGMT 患者的生存结果无差异 ( = 0.12)。

结论

根据我们的经验,未甲基化-MGMT 的 GB 患者从 RT 联合 TMZ 的适度递增剂量中获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/969c/5660746/dded5cdb8640/BMRI2017-9461402.001.jpg

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