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.
Highlights
Glioblastoma is the most frequent primary brain tumor (≥50% out of all the cases of primary tumors in the brain) with an incidence of about five new cases per 100,000 per year
Out of the 117 patients selected for this study, the methylguanine-DNA methyltransferase (MGMT) promoter methylation status was, respectively, methylated and unmethylated in 48 (41%) and in 69 patients (59%)
The multivariate analysis confirmed that Karnofsky Performance Status (KPS) = 70 (HR: 2,424; 95% CI: 1,082–3,652; p = 0,001) and B-subtotal resection (STR) (HR: 1,783; 95% CI: 1,451–4,449; p = 0,001) and unmeth-MGMT status (HR: 3,088; 95% CI: 1,887–5,054; p = 0,001) were independently associated with a shorter Overall Survival (OS) and Progression-Disease Free Survival (PDFS)
Summary
Glioblastoma is the most frequent primary brain tumor (≥50% out of all the cases of primary tumors in the brain) with an incidence of about five new cases per 100,000 per year. The prognosis of this disease remains poor with 5-year survival outcomes barely reaching 5%. Postsurgery RT plus TMZ chemotherapy is presently the backbone of the management of patients affected by GB [1]. In the clinical setting only the methylation status of the O(6)methylguanine-DNA methyltransferase (MGMT) promoter, that is, a DNA repair enzyme that causes resistance to alkylating agents such as TMZ [4, 5], plays a practical role. The MGMT promoter methylation positive status has a highly significant predictive role of response to TMZ combined with RT [1, 5], whereas unmethylated MGM is considered an inherent prognostic indicator for patients with GB with a poor survival [6, 7]. A more limited positive impact on survival results of the RT and TMZ
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