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. 2017:2017:9461402.
doi: 10.1155/2017/9461402. Epub 2017 Oct 12.

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

Paolo Tini  1   2 , Valerio Nardone  2 , Pierpaolo Pastina  3 , Giuseppe Battaglia  3 , Clelia Miracco  3   4 , Lucio Sebaste  2 , Giovanni Rubino  2 , Alfonso Cerase  5 , Luigi Pirtoli  2   3
Affiliations

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

Paolo Tini et al. Biomed Res Int. 2017.

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 (p = 0,01) and PDFS (p = 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 (p = 0,12).

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

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Figures

Figure 1
Figure 1
Anatomical distribution and GTV volume (expressed in cm3) of GB lesions treated with different RT dose scheme (chi-square test; p = 0,41) in methylated (a) and unmethylated (b) patients.
Figure 2
Figure 2
Overall Survival (a) and Progression-Disease Free Survival (b) (Kaplan-Meier method) according to standard (SDRT-TMZ) versus escalated (HDRT-TMZ) RT dose (log-rank test p value < 0,05) in unmethylated patients.
Figure 3
Figure 3
Overall Survival (a) and Progression-Disease Free Survival (b) (Kaplan-Meier method) according to standard (SDRT-TMZ) versus escalated (HDRT-TMZ) RT dose (log-rank test p value < 0,05) in unmethylated patients with incomplete resection.
See this image and copyright information in PMC

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