A large prospective Italian population study (Project of Emilia-Romagna Region in Neuro-Oncology; PERNO) in newly diagnosed GBM patients (pts): Outcome analysis and correlations with MGMT methylation status in the elderly population.

Abstract

2021 Background: The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly pts with GBM remains unclear. We therefore evaluated the efficacy of this approach in pts >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. Methods: The criteria for selecting pts enrolled in the PERNO study were: age >70 years; PS 0-3; histologically confirmed GBM; postoperative radiotherapy after surgery; residence in the Emilia Romagna region. Data were collected prospectively. Results: Pts accrual, started on January 1 2009, was closed, as planned, on December 31 2010. In the pts enrolled (n=53), median overall survival (mOS) was 11.1 months (95% CI: 8.8 - 13.5); survival rates at 1-, 2- and 3-years were 41.5% (95% CI: 28.2 – 54.8%), 15.2% (95% CI: 4.8 – 25.6%) and 6.1% (95%CI: 0 – 15.9%), respectively. Twenty-eight pts received RT/TMZ, and 25 pts RT alone. mOS was 11.6 months (95% CI: 8.6 – 14.6) following RT/TMZ and 9.3 months (95% CI: 8.1 – 10.6) following RT alone. mOS for pts with MGMT methylated status (n = 17) was 13.5 months (95% CI: 7.7 – 19.2), being 17.2 months (95% CI: 11.5 - 22.9) in those treated with RT/TMZ (n = 6) and 8.8 months (95% CI: 2 – 15.6) in those treated with RT alone (n = 11, p = 0.09). Elderly pts with MGMT unmethylated status (n = 25) had a mOS of 8.5 months (95% CI: 6 – 11, p = 0.014), being 8.5 months (95% CI: 2.3 – 14.7) in pts treated with RT/TMZ (n =10), and 8 months (95% CI: 3 – 12.9) in those treated with RT (n = 15, p = 0.55). Conclusions: RT/TMZ appears to be more effective in prolonging the mOS of elderly pts in those with MGMT methylation status (17.2 vs 8.5 months), and seem to perform better than TMZ alone, for which mOS was 9.7 months in the Nordic phase III trial. These findings underline the value of the ongoing randomized EORTC 26062-22061/NCIC CE.6 phase III comparing RT/TMZ with short course RT alone.

The Predictive but Not Prognostic Value of MGMT Promoter Methylation Status in Elderly Glioblastoma Patients: A Meta-Analysis

“…With the above eligibility criteria, 16 studies [20] – [35] were identified (2 phase III trials [24] – [25] , 3 phase II trials [26] , [31] , [33] , 4 prospective cohort studies [22] – [23] , [34] – [35] and 7 retrospective cohort studies [20] – [21] , [27] – [30] , [32] ; Fig. 1 ).…”

“…1 ). Of those, 4 studies [20] – [22] , [35] were published in abstract. Characteristics of the identified studies were summarized in Table 1 .…”

“…The cutoff age for elderly patients was defined variably across the studies, among which seven studies set the age cutoff at 65 years [20] – [21] , [25] , [27] , [30] – [31] , [34] , seven studies set the cutoff at 70 years [22] – [23] , [26] , [28] , [32] – [33] , [35] and one study set the cutoff at 80 years [29] . Besides, one study with an inclusion criterion of 60 years or over was also included because most of their patients were eligible for our study [24] .…”

“…Regarding the treatment, a number of adjuvant therapies were utilized in the studies such as supportive care, TMZ alone, RT alone and RT in combination with TMZ or carmustine wafer. [20] – [35] …”

“…Three studies were [20] – [22] finally excluded from the quantitative analyses, from which the HRs could not be extracted. Thus an assessment of risk of bias was performed on the remaining 13 studies using the customized domain-based NOS [23] – [35] . The assessment showed no apparent variations across the studies in most domains of bias, except for selection bias.…”